Breast Clinical Trials

Trial MenuList of Available Trials:

 

CINJOG 040406: “Effect of DNA Variations on Breast Cancer Risk and Recurrence. A Study of The Cancer Institute of New Jersey Oncology Group (CINJOG)”

ELIGIBILITY:

  • Evaluation in surgical/medical/radiation oncology/radiology clinic, high risk clinic, or survivors clinic with a history of one of the following:
    • Previous biopsy-confirmed diagnosis of breast cancer including DCIS and invasive ductal carcinoma OR

    • Previous biopsy-confirmed diagnosis of the marker of increased risk of developing breast cancer LCIS or atypical hyperplasia OR

    • Previous biopsy-confirmed diagnosis of benign breast conditions (includes fibrocystic changes, fibroadenoma) with no prior diagnosis of breast cancer OR

    • Individual participating as a healthy volunteer.
       
  • Willing to undergo venipuncture to obtain 20 ml of blood, and submission of a case report form.

  • Age > 18 years.

ENROLLMENT TARGET: 10,000 - *Enrollment is 4107 as of 11/2013

Back to top

CINJOG 040803: “Phase I/II Study of Weekly Abraxane and RAD001 in Women with Locally Advanced or Metastatic Breast Cancer. A Study of The Cancer Institute of New Jersey Oncology Group (CINJOG)”

ELIGIBILITY:

  • Adult women (≥ 18 years of age) with metastatic or locally recurrent breast cancer, not amenable to treatment by surgery or radiotherapy

  • Histological confirmation of breast cancer that is Her2/neu negative

  • Patients may not have received prior chemotherapy for metastatic breast cancer. Prior adjuvant chemotherapy is allowed.

  • Patients may have received prior systemic endocrine treatment for advanced breast cancer (i.e. metastatic or locally recurrent breast cancer, not amenable to treatment by surgery or radiotherapy).

  • Patients must have at least one measurable lesion. Measurable disease documented and defined as by RECIST criteria (see Section 9). Baseline measurements must be obtained within 4 weeks prior to enrollment.

  • NOTE: As the only exception regarding the requirement for at least one measurable lesion, patients with bone metastases as the sole site of disease can be included, provided they have at least 2 lytic bone lesions, detected by either X-Ray, CT scan or MRI.

  • Prior radiation therapy allowed to < 25% of the bone marrow and patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.

  • Patients must have an ECOG performance status ≤ 2 (Appendix B).

  • Patients on antiangiogenic agents are not excluded from this study.

  • Patients must have normal organ and marrow function as defined below:
    • ANC ≥ 1.5 x 109 cells/L,

    • Platelets ≥ 100 x 109 cells/L,

    • Hb >9 g/dL,

    • Serum Bilirubin ≤ 1.5 x ULN,

    • Absence of ascites and encephalopathy due to liver disease,

    • INR < 1.5 x ULN,

    • ALT and AST, ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases).

    • Serum Creatinine ≤ 1.5 mg/Dl,

    • Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN,

    • In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy.
       
  • Estimated life expectancy of at least 3 months.

ENROLLMENT TARGET: 72 - *Enrollment is 26 as of 11/2013

Back to top

SCUSF 0806: “Phase II Placebo-controlled Trial of Lisinopril and Coreg CR to Reduce Cardiotoxicity in Patients with Breast Cancer Receiving (neo)Adjuvant Chemotherapy with Trastuzumab (Herceptin)”

Summary:

Rationale:
Lisinopril or carvedilol phosphate may help reduce side effects caused by trastuzumab. It is not yet known whether lisinopril or carvedilol phosphate is more effective than a placebo in reducing side effects caused by trastuzumab.

Purpose:
This phase II trial is studying lisinopril and carvedilol phosphate to see how well they work compared with a placebo in reducing side effects in patients with HER2-positive breast cancer receiving trastuzumab.

Outline:
This is a multicenter study. Patients are stratified according to chemotherapy comprising an anthracycline (yes vs. no). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive oral lisinopril once daily.
  • Arm II: Patients receive oral carvedilol phosphate extended-release once daily.
  • Arm III: Patients receive oral placebo once daily. In all arms, study treatment begins with the first dose of trastuzumab and continues for up to 52 weeks or until the end of trastuzumab therapy.

-Quality of life is assessed using the EORTC QLQ-C30 questionnaire at baseline, at 52 weeks (or at the end of trastuzumab therapy), and at 18 and 24 months (or 6 and 12 months after the completion of trastuzumab).

-After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

ELIGIBILITY:

DISEASE CHARACTERISTICS:

  • Ambulatory, early stage (I or II) breast and prostate cancer survivors who are at least two years out of treatment (excluding hormonal therapy) with no severe co-morbid conditions (e.g., congestive heart failure, myocardial infarction, angina) that require extensive coordination of specialist care are eligible.
  • Diagnosis of HER2-positive breast cancer
  • Scheduled to receive adjuvant or neoadjuvant trastuzumab therapy
  • Anthracycline-containing regimens allowed
  • Patients receive trastuzumab with their chemotherapy allowed for eligibility work-up
  • Taxanes are allowed
  • Trastuzumab therapy may be given with or after primary chemotherapy
  • Pertuzumab may be used in conjunction with trastuzumab
  • No metastatic disease
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • LVEF ≥ 50% by MUGA or ECHO
  • Creatinine ≤ 1.2 mg/dL
  • Sitting systolic BP > 90 mm Hg
  • Pulse ≥ 60 beats/minute
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow capsules

  • Adequate renal function for administration of trastuzumab-containing chemotherapy regimen
  • No known cardiac history (i.e., heart failure, myocardial infarction, or radiation-induced cardiac dysfunction)
  • No known allergy to either ACE inhibitors or β-blockers
  • No history of bronchial asthma or related bronchospastic conditions
  • No hereditary or idiopathic angioedema
  • No history of severe hypersensitivity reactions to drugs or other causes (e.g., bee stings)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior trastuzumab or anthracyclines prior to this chemotherapy regimen
  • No current treatment with other angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), such as losartan, β-blockers, or digoxin
  • Concurrent participation in other investigational studies allowed

OBJECTIVES:

Primary

  • To determine if administration of lisinopril or carvedilol phosphate extended-release (compared to placebo) will reduce the incidence of trastuzumab-induced cardiotoxicity, as measured by LVEF, in women receiving adjuvant or neoadjuvant trastuzumab for HER2-positive breast cancer.

Secondary

  • To determine whether patients randomized to receive lisinopril or carvedilol phosphate extended-release have fewer interruptions in trastuzumab therapy due to cardiomyopathy.
  • To determine whether the treatment effect is consistent in anthracycline and nonanthracycline patient cohorts.
  • To determine changes in quality of life (QOL) in patients treated with these regimens.
  • To determine the long-term effects of lisinopril and/or carvedilol phosphate extended-release on the prevention of cardiomyopathy and their impact on QOL.
  • To compare the predictive value of troponin I and BNP in the identification of trastuzumab-induced cardiotoxicity.

National Enrollment to Date: 355/468

Back to top

ECOG 2108: “A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Women with Metastatic Breast Cancer”

OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs. ER+ or PR+, and HER2-, chemotherapy and/or endocrine therapy vs. ER- or PR-, and HER2- vs. HER2+), and number of involved organ systems with distant disease (regional nodes in the maxillary, supraclavicular, and internal mammary locations are not considered distant sites) (1 vs. > 1). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.
  • Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.

-Patients may undergo blood and tumor tissue sample collection for circulating tumor cells (CTC) burden and future studies.

-Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life questionnaires at baseline and periodically during study.

-After completion of study therapy, patients are followed up periodically for 5 years.

ELIGIBILITY:

DISEASE CHARACTERISTICS:

  • Diagnosis of intact primary (not recurrent) invasive carcinoma of the breast
  • Stage IV disease
  • Confirmation of the primary tumor should be by needle biopsy (preferred)
  • Incisional surgical biopsy allowed as long as there is residual palpable or tumor image in the breast
  • Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated)
  • For women not undergoing maxillary dissection, sentinel node biopsy should document an maxillary nodal burden of 1-2 involved lymph nodes (i.e., ACOSOG Z-11 criteria may be applied)
  • Prior non-invasive (DCIS) cancer allowed provided there has been no recurrence
  • Prior ipsilateral invasive cancer allowed if more than 5 years previous
  • No synchronous contralateral breast cancer
  • Patients should have at least one organ system involved with distant metastatic disease
  • If patient has only one metastatic lesion/focus, this must be proven by biopsy and the pathology report confirming the diagnosis of primary breast cancer, as well as the metastatic site, must be available
  • Must have available radiologic reports documenting disease status within the past 6 weeks prior to initiating systemic therapy
  • CNS metastases allowed provided projected survival > 6 months
  • Patients must have completed at least 16 weeks of optimal systemic therapy (appropriate to the tumor biological profile and the patient's age and menopausal status)
  • If systemic therapy is discontinued for toxicity, but there is no distant progression and at least 12 weeks of therapy have been delivered, then the patient remains eligible
  • Radiation therapy (if indicated) must begin within 12 weeks of final therapeutic surgical procedure (including re-excision for free margins and completion of maxillary dissection)

  • Patients may register at any time from the time of diagnosis of stage IV breast cancer (if eligibility criteria met) to the time when a maximum of 30 weeks of induction systemic therapy has been completed
  • Patients must be randomized within 16-32 weeks after the start of systemic therapy
  • Patients must not have experienced disease progression since the start of systemic therapy, as evidenced by radiographic documentation of disease status before treatment and within 4 weeks +/- 2 weeks prior to randomization, including:
  • No new sites of disease
  • No enlargement of existing sites by 20% or more in longest diameter
  • No symptomatic deterioration
  • Patients who require radiotherapy to bone metastases during induction systemic therapy are eligible
  • Local disease at the primary site must be asymptomatic
  • Hormone receptor status known

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Menopausal status not specified
  • Patients must have adequate organ function to undergo local therapy 4 weeks +/- 2 weeks prior to randomization per investigator discretion and institutional guidelines
  • More than 5 years since other primary cancers that were curatively treated
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use an accepted and effective contraception method

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

OBJECTIVES:

Primary

  • To evaluate whether early local therapy comprising surgery of intact primary disease compared to local palliative therapy only in patients with stage IV breast cancer, whose disease does not progress during initial optimal systemic therapy, will result in prolonged survival.

Secondary

  • To compare the time to uncontrolled chest wall disease between patients treated with these regimens.
  • To determine whether there is a difference in health-related quality-of-life (HRQOL) between patients treated with these regimens.
  • To determine whether the absolute value of circulating tumor cells (CTC) burden at 6 months following randomization (time +6) will be lower in the palliative therapy arm than in early local therapy arm, and whether this value is inversely related to survival (lower CTC, longer survival).
  • To collect tumor and blood specimens for future exploration of the biological interactions between the primary tumor and metastatic lesions and the effect of primary tumor resection.

National Enrollment to Date: 165/368

Back to top

Please contact CINJ before opening/enrolling patients on this trial

NSABP B-43: “A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently with Radiation Therapy and Radiation Therapy Alone for Women with HER2‑Positive Ductal Carcinoma in Situ Resected by Lumpectomy”

ELIGIBILITY:

  • On histologic examination, the tumor must be ductal carcinoma in situ (DCIS). (Patients with mixed DCIS and lobular carcinoma in situ [LCIS] are eligible.)

  • The DCIS must be HER2-positive as determined by central testing. Central testing to determine HER2 status: Central testing for determination of HER2 status will be performed at a central reference lab according to the ASCO College of American Pathologists (CAP) guidelines and supervised by K.P. Siziopikou, MD, PhD, Director of Breast Pathology, RUMC. HER2 amplification status for B-43 will be evaluated by IHC using the HercepTest® (Dako, Carpinteria, CA) for all cases; cases with a 1+ or 2+ IHC reading will be reflexed to FISH (PathVysion®, HER2 DNA probe kit, by Vysis, Inc, Downers Grove, IL). A 0 or 3+ IHC reading will be considered final for eligibility. As part of the correlative science in B-43, FISH testing will also be performed for all cases (enrolled patients) at a later date.

  • Estrogen and/or progesterone receptor status must be determined prior to randomization. (Patients with DCIS that is hormone receptor positive or negative are eligible.)

  • All DCIS must have been resected by lumpectomy.

  • The margins of the resected specimen must be histologically free of DCIS. For patients in whom pathologic examination demonstrates DCIS present at the line of resection, re‑excision(s) may be performed to obtain clear margins. (Patients who require mastectomy are not eligible.)

  • If maxillary staging is performed, nodal staging must be pN0, pN0(i-), pN0(i+) which is defined as isolated tumor cells ≤ 0.2 mm, regardless of the method of detection, i.e., IHC or H&E, pN0(mol-), or pN0(mol+). NOTE: Axillary staging is not required. (Refer to AJCC Staging Criteria in the Treatment Trial Information section in the Members’ Area of the NSABP Web site for TNM nomenclature and staging information.)

  • The interval between the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins) and randomization must be no more than 120 days.

National Enrollment to Date:  1498/2000

Please contact CINJ before opening/enrolling patients on this trial

Back to top

Please contact CINJ before opening/enrolling patients on this trial

NSABP B-47: “A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of TC or Four Cycles of AC Followed by Four Cycles of Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women with Node-Positive or High-Risk Node-Negative HER2-Normal Invasive Breast Cancer”

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining [group 1] vs. HER2/neu 0 or 1+ staining [group 2]).

GROUP I: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab (Herceptin®) IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22‑26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1.

-After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1 year, every 4 months for 1 year, every month for 3 years, and then annually thereafter.

ELIGIBILITY:

  • Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of the bladder
  • Histologic evidence of muscularis propria invasion
  • Meets 1 of the following stage criteria:
  • Stage T2-4a; NX, N0, or N1; and M0 disease
  • Clinical stage T1, grade 3/3 disease AND requires definitive local therapy
  • Tumor involvement of the prostatic urethra allowed provided the following criteria are met:
  • Tumor was visibly completely resected
  • No evidence of stromal invasion of the prostate
  • No evidence of distant metastases by chest x-ray or CT scan AND abdominal/pelvic CT scan
  • Has undergone transurethral bladder resection (as thorough as is judged safely possible) within the past 3-8 weeks, including bimanual examination with tumor mapping
  • Sufficient tumor tissue available for HER2/neu analysis
  • Not a candidate for radical cystectomy
  • Performance status - Zubrod 0-2
  • Absolute neutrophil count >= 1,800/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 8.0 g/dL (transfusion or other intervention allowed)
  • Bilirubin < 2.0 mg/dL
  • SGOT and SGPT < 2.5 times upper limit of normal
  • No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Creatinine =< 3.0 mg/dL
  • LVEF >= 40% by MUGA scan or echocardiogram
  • No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • No transmural myocardial infarction within the past 6 months
  • Not pregnant or nursing
  • No nursing for 6 months after completion of study treatment (for patients receiving trastuzumab [Herceptin®])
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • Able to tolerate systemic chemotherapy and pelvic radiotherapy
  • No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
  • No history of allergic reaction to study drugs
  • No history of inflammatory bowel disease
  • No acute bacterial or fungal infection requiring IV antibiotics
  • No AIDS
  • No other severe active comorbidity
  • No prior systemic chemotherapy with anthracyclines or taxanes
  • No prior systemic chemotherapy for TCC
  • No prior pelvic radiotherapy

PRIMARY OBJECTIVE:

I.    Determine the acute toxicity of paclitaxel and radiotherapy with or without trastuzumab (Herceptin®) in patients who have undergone prior transurethral bladder resection for muscle-invasive transitional cell carcinoma of the bladder.

SECONDARY OBJECTIVES:

  1. Determine the ability of these patients to complete these regimens.
  2. Determine the efficacy of these regimens, in terms of achieving a complete response of the primary tumor, in these patients.

    Determine the 5-year disease-free and overall survival of patients treated with these regimens.

  3. Determine the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival of patients treated with these regimens.

National Enrollment to Date: 2179/3260

Please contact CINJ before opening/enrolling patients on this trial

Back to top

RTOG 1005: “A Phase III Trial of Accelerated Whole Breast Irradiation with Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer”

***The cosmesis subset for patients not receiving chemotherapy has met its accrual and will be closed to further enrollment at close of business on Friday March 8th, 2013. The trial as a whole still remains open to accrual.***

 

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50 years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within 9 weeks of last surgery or chemotherapy delivery.

  • Arm I: Patients undergo standard whole-breast radiotherapy (WBI) comprising intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) 5 days a week for 3-5 weeks followed by a sequential radiotherapy boost to the lumpectomy area 5 days a week for 1-1½ weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo accelerated hypofractionated WBI comprising IMRT or 3D-CRT with a concurrent boost to the lumpectomy area 5 days a week for 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

-Patients' tissue samples may be collected for future research studies.

-After completion of study therapy, patients are followed up for 1 month, at 6 months, and then yearly.

ELIGIBILITY:

DISEASE CHARACTERISTICS:

  • Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole-breast irradiation (WBI) with boost without regional nodal irradiation planned
  • Must meet one of the following criteria:
  • Stage I or II breast cancer AND at least one of the following:
  • Age < 50 years
  • Positive maxillary nodes
  • Lymphovascular space invasion (LVI)
  • At least 2 close resection margins (> 0 mm to ≤ 2 mm)
  • One close resection margin and extensive in-situ component (EIC)
  • Focally positive resection margins
  • Non-hormone-sensitive breast cancer (estrogen-receptor negative (ER-) and progesterone-receptor (PR-) negative)
  • Grade III histology
  • Oncotype recurrence score > 25
  • Stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age < 50 years
  • No DCIS and age > 50 years
  • No DCIS and age < 50 years and nuclear grade 1 or 2
  • Resected by lumpectomy after neoadjuvant systemic therapy
  • If multifocal breast cancer, then it must have been resected through a single lumpectomy incision with negative margins
  • Breast-conserving surgery with margins defined as follows:
  • Negative margins defined as no tumor at the resected specimen edge
  • Close resection margins > 0 mm to ≤ 2 mm as follows:
  • One close resection margin and EIC
  • Two or more close resection margins
  • A focally positive resection margin
  • Allowable options for mandatory maxillary staging include:
  • Sentinel node biopsy alone (if sentinel node is negative, pN0, pN0[IHC-,+])

  • Sentinel node biopsy alone, or followed by maxillary node dissection, for clinically node-negative patients as described below:
  • Microscopic sentinel node (SN) positive (pN1mic)
  • One or two SNs positive (pN1) without extracapsular extension
  • Negative SN biopsy after neoadjuvant chemotherapy
  • SN biopsy followed by maxillary dissection with a minimum total of 6 maxillary nodes if any of the following exist:
  • > 2 positive SN
  • Solitary SN that is positive without other sentinel nodes dissected
  • Clinically (by either imaging or examination) T3 disease
  • Presence of one or more positive SNs with extracapsular extension, clinically node-positive disease, or LVI in the primary tumor
  • Axillary dissection alone (with a minimum of 6 maxillary nodes)
  • CT-imaging of the ipsilateral breast within 28 days of study entry for the radiation treatment planning
  • Must be able to delineate on CT scan the extent of the target lumpectomy cavity for boost (placement of surgical clips to assist in treatment planning of the boost is strongly recommended)
  • No clinical evidence for distant metastases, based upon the following minimum diagnostic workup:
  • History/physical examination, including breast exam (inspection and palpation of the breasts) and documentation of weight and Zubrod Performance Status of 0-2 within 28 days prior to study entry
  • Bilateral mammogram within 90 days prior to study entry
  • Bilateral or right and left mammography within 90 days prior to neoadjuvant chemotherapy, diagnostic biopsy establishing diagnosis, or last surgery (breast or axilla)
  • No prior invasive or in-situ carcinoma of the breast (prior LCIS is eligible)
  • No American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, or M1 breast cancer
  • Must not have two or more breast cancers that are not resectable through a single lumpectomy incision
  • No invasive breast cancer and low-risk (see low risk features below) for 5-year in-breast recurrence after lumpectomy with negative margins, defined as:
  • ≥ 70 years old, T1, N0, ER/PR+
  • > 50 years old, T1, N0, grade 1-2 breast cancer, ER/PR+
  • No suspicious unresected microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
  • No non-epithelial breast malignancies such as sarcoma or lymphoma
  • No Paget disease of the nipple
  • No male breast cancer
  • Breast implants allowed

PATIENT CHARACTERISTICS:

  • ANC ≥ 1,800/mm³
  • Platelet count ≥ 75,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
  • Negative serum pregnancy test within 14 days of study entry
  • Women of childbearing potential must not be pregnant or nursing and willing to use medically acceptable form of contraception during radiotherapy
  • No prior invasive non-breast malignancy (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
  • No severely active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
  • Acquired Immune-Deficiency Syndrome (AIDS) based upon current CDC definition
  • HIV testing is not required for entry into this protocol
  • No active systemic lupus, erythematosus, or any history of scleroderma or dermatomyositis with active rash
  • Medical, psychiatric, or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Study entry must be within 50 days of last breast/maxillary surgery and/or last chemotherapy
  • No treatment plan that includes regional-node radiotherapy
  • No prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation therapy fields
  • No intention to administer concurrent chemotherapy for current breast cancer

OBJECTIVES:

Primary

  • To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.

Secondary

  • To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost.
  • To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and NTCP calculations.
  • To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity.
  • To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost.
  • To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI.
  • If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
  • To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost

National Enrollment to Date: 1576/2312

Back to top

SWOG S1007: “A Phase III Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer with Recurrence Score (RS) of 25 or Less”

OUTLINE: This is a multicenter study. Patients are stratified according to Recurrence Score (0-13 vs. 14-25), menopausal status (pre-menopausal vs. post-menopausal), and type of nodal dissection (maxillary lymph node dissection [with or without sentinel node mapping] vs. sentinel node biopsy without maxillary lymph node dissection). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.

-Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and periodically during study. Information on Medicare and/or insurance coverage and on health coverage decisions may also be collected periodically.

-After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for at least 15 years.

ELIGIBILITY:

  • Histologically confirmed invasive breast cancer

  • 1-3 node-positive disease (pN1mi, pN1a, pN1b, or pN1c) by sentinel node biopsy or maxillary lymph node dissection
  • Positive estrogen receptor (ER) and/or progesterone receptor (PR) status according to American Society of Clinical Research/College of American Pathologists (ASCO/CAP) guidelines
  • Considered positive if >= 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal [normal epithelial elements] and external controls
  • Negative HER-2 as determined by IHC or non-amplified fluorescence in situ hybridization (FISH) for screening
  • If HER2 is 2+ by IHC, FISH must be performed and must not be positive (must be a ratio of =< 2.2)
  • If IHC is 0 or 1+ by institutional standards, FISH is not required
  • Patients with FISH in the indeterminate range (a ratio of 1.8 to 2.2) allowed provided they are not planning to receive treatment with trastuzumab
  • Recurrence Score (RS) by Oncotype DX =< 25
  • Submission of tissue (paraffin block from primary tumor, positive and negative lymph node block) from surgery required
  • Prior diagnosis of DCIS allowed provided it was treated with mastectomy alone (no therapeutic radiation or endocrine therapy)
  • No inflammatory breast cancer or metastatic disease
  • Must have had breast-conserving surgery with planned radiotherapy or total mastectomy (with or without planned post mastectomy radiation) with clear margins within the past 28-84 days
  • Menopausal status: pre- or post-menopausal
  • Zubrod performance status 0-2
  • Not pregnant or nursing
  • Fertile patients must use an effective non-hormonal contraception method while on treatment and for ≥ 3 months after completion of protocol treatment
  • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage 0, I, or II cancer from which the patient is currently in complete remission; or any other cancer from which the patient has been disease-free for the past 5 years
  • LVEF ≥ 50% if an anthracycline-based regimen is planned
  • Patients randomized to chemotherapy may also co-enroll in Phase III trials that compare chemotherapies
  • No prior chemotherapy or endocrine therapy for breast cancer
  • No prior preventive tamoxifen or raloxifene
  • No prior therapeutic breast radiotherapy
  • Not requiring concurrent chronic treatment with systemic steroids or other immunosuppressive agents
  • Patients randomized to either arm may also co-enroll in Phase III trials that compare local therapies or compare systemic therapies (not including chemotherapy)

PRIMARY OBJECTIVES:

I. To determine the effect of endocrine therapy with versus without chemotherapy in patients with node-positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX®.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS), distant disease-free survival (DDFS), and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.

II. To compare the toxicity across the treatment arms.

III. To perform other assays or tests (in particular the PAM50 risk of relapse score) as they are developed and validated that measure potential benefit of chemotherapy and compare them to Oncotype DX®.

IV. To determine the impact of management with Oncotype DX® on patient-reported anxiety (co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after disclosure of test results, and during the randomized trial.

V. To determine the impact of Oncotype DX® on the initial management cost of node-positive, HR-positive, HER2-negative breast cancer.

VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy versus no chemotherapy.

VII. To estimate the cost-effectiveness of management with Oncotype DX® vs. usual care using modeling and DFS information from the trial.

VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and LDFI of patients randomized to chemotherapy versus no chemotherapy.

IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).

X. To determine the impact of management with Oncotype DX® on patient-reported decision conflict, perceptions regarding Oncotype DX® testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes).

National Enrollment to Date: 1941/4000

Back to top