Lung Clinical Trials

Trial MenuList of Available Trials:

 


CINJOG 031105: “
Modulation of Autophagy with Hydroxychloroquine in Patients with Advanced/recurrent Non‑Small Cell Lung Cancer – A Phase II Study. A Study of The Cancer Institute of New Jersey (CINJOG).”

ELIGIBILITY:

Cancer Criteria:

  • Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirate or biopsy. Sputum cytology alone is not sufficient.

  • Advanced stage NSCLC (stage IVa ((malignant pleural effusion (is now staged as stage IVa by the most recent staging system), or stage IV, or recurrent disease)).

  • Measurable disease according to RECIST criteria.

  • Patient with CNS metastasis are required to have stable disease documented by being off treatment (surgery, radiation therapy) for at least 2 weeks, and four (4) weeks is preferred. A contrast enhanced brain CT or brain MRI is required within 35 days of enrollment. Patients with brain metastases who qualify for protocol therapy will be included in Cohort 2 (ineligible for treatment with Bevacizumab).

  • No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting. Post-operative adjuvant therapy for previously resected NSCLC is allowed as long as the last dose was given greater than 1 year before study entry, and there is current evidence of disease progression.

  • Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks before treatment and provided that all radiation-related toxicities have resolved to≤ Grade 1.

  • No active malignancy other than NSCLC. Patients with a history of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast within the past 3 years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for > 3 years.

Laboratory Requirements:

  • Adequate organ function, as evidenced by ALL the following:
    • absolute neutrophil count (ANC) ≥ 1500/mm³

    • platelet count ≥ 100,000/mm³

    • hemoglobin ≥ 9 gm/dL

    • total bilirubin ≤ 1.5 x ULN; if patient has Gilbert’s disease, then patient must have isolated hyperbilirubinemia (e.g. no other liver function test abnormality), with maximum bilirubin ≤ 2 X institutional ULN.

    • AST and ALT ≤ 2.5 x ULN in the absence of liver metastases; AST and ALT ≤ 5 x ULN in the presence of liver metastases
    • alkaline phosphatase ≤ 2.5 x ULN
    • creatinine ≤ 1.5 X institutional ULN or calculated creatinine clearance ≥ 60 ml/min as estimated using the Cockroft-Gault formula.

Comorbidities:

For Cohort 1: (Bevacizumab eligible):

  • No history of gross hemoptysis (defined as bright red blood of a half-teaspoon or more) within 3 months prior to enrollment.

  • None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.

For patients who have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipate the need for such while on active treatment, may participate and receive Bevacizumab at the start of the second or third cycle as they would under standard care. Placement of vascular access device is not considered major surgery, but the incision must have healed before initiation of treatment.

  • Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2 (see Appendix B of the protocol).

  • No history of significant vascular disease (e.g. aortic aneurysm).

  • No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.

  • Adequate organ function
    • INR ≤ 1.5 and aPTT WNL.

    • Urine Protein Creatinine (UPC) ratio < 1.0 or 24 hour urine protein ratio < 1000 mg

UPC ratio of spot urine is an estimation of the 24 urine protein excretion. A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. To obtain a UPC ratio:

  • Obtain at least 4 mL of a random urine sample

  • Determine protein and creatinine concentration

  • Calculate the UPC using one of the following formulae

[urine protein]/[urine creatinine] – if both values are reported in mg/dL

[(urine protein) x 0.088]/[urine creatinine] – if urine creatinine is reported in mmol/L

For Cohort 2 (Bevacizumab ineligible):

  • None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.

  • Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2 (see Appendix B of the protocol).

  • No history of significant vascular disease (e.g. aortic aneurysm).

For ALL (Cohort 1 and Cohort 2):

  • Patients must not have psoriasis or porphyria.

  • No known hypersensitivity to 4-aminoquinoline compound.

  • Patients must not have known or suspected G-6P deficiency.

  • No know bleeding diathesis or coagulopathy.

  • No known GI pathology that would interfere with drug bioavailability.

  • No peripheral or sensory neuropathy > Grade 1 at study entry.

  • No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab or hydroxychloroquine or any of their components.

  • No ongoing or active infection at study entry.

  • Patients must not be receiving treatment for rheumatoid arthritis or systemic lupus erythematosus.

  • Patients must not have HIV or be taking HAART therapy.

  • Patients must not have a history of any condition (social or medical) that, in the opinion of the Investigator, might interfere with the patient’s compliance with the protocol or pose additional or unacceptable risk to the patient.

  • Women must NOT be pregnant or breastfeeding.

  • Women must :
    • Have a negative serum or urine pregnancy test within 7 days prior to study entry if she is a woman of child-bearing potential, OR
    • Be at least one year post-menopausal, OR
    • Be surgically sterile
       
  • Patients of childbearing or child fathering potential must be willing to use an acceptable method of birth control prior to study entry and for the duration of the study. Acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence.

  • Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria.

ENROLLMENT TARGET: 40 - *Enrollment is 18 as of 11/2013

Back to top

CALGB 30610: “Phase III Comparison of Thoracic Radiotherapy Regimens in Patients with Limited Small Cell Lung Cancer also Receiving Cisplatin and Etoposide”

Outline:
This is a 2-part, multicenter, randomized study. Patients are stratified according to gender, weight loss 6 months prior to study entry (≤ 5% of body weight vs. > 5% of body weight), ECOG performance status (0 vs. 1 vs. 2), radiotherapy technique (intensity-modulated radiotherapy vs. 3-dimensional conformal radiotherapy), and radiotherapy start time (at first course of protocol chemotherapy, after one course of prior non-protocol chemotherapy vs. at first course of protocol chemotherapy, without prior non-protocol chemotherapy vs. at second course of protocol chemotherapy, without prior non-protocol chemotherapy).

  • Part 1: Patients are randomized to 1 of 3 treatment arms.
    • Arm I: Patients undergo standard-dose (45 Gy given in 30 treatments) thoracic radiotherapy twice daily, 5 days a week, for 3 weeks. Patients also receive cisplatin IV on day 1 and etoposide IV on days 1, 2, and 3.

    • Arm II: Patients undergo higher-dose (70 Gy given in 35 treatments) thoracic radiotherapy once daily, 5 days a week, for 7 weeks. Patients also receive cisplatin and etoposide as in arm I.

    • Arm III: (discontinued as of 01/15/13) Patients undergo higher-dose (61.2 Gy given in 34 treatments) thoracic radiotherapy once daily, 5 days a week, during the initial 16 days (approximately 3 weeks) of treatment and then twice daily, 5 days a week, for the final 9 days (approximately 2 weeks) of treatment. Patients also receive cisplatin and etoposide as in arm I.

In all arms, treatment with cisplatin and etoposide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

  • Part 2: An interim analysis, conducted after accrual of 30 patients per arm, will select one experimental arm based upon a comparison of treatment-related toxicity. The most toxic experimental arm will be discontinued, and the trial will continue comparing standard therapy (arm I) to the selected experimental regimen (arm II) as in part 1.

Prophylactic Radiotherapy: Within 3-6 weeks after completion of chemotherapy, patients with responding disease are eligible to undergo prophylactic radiotherapy to the brain once a day, 5 days a week, for 2 weeks.

-After completion of study treatment, patients are followed up at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years or until disease progression. At disease progression, patients are followed up every 6 months.

ELIGIBILITY:

DISEASE CHARACTERISTIS:

  • Histologically or cytologically confirmed small cell lung cancer (SCLC)
    • Limited-stage disease
      • Disease restricted to one hemithorax with regional lymph node metastases, including ipsilateral hilar, ipsilateral and contralateral mediastinal, and ipsilateral supraclavicular lymph nodes
  • The following patients are not eligible:
    • Patients with disease involvement of the contralateral hilar or supraclavicular lymph nodes

    • Patients with pleural effusions that are visible on plain chest radiographs, whether cytologically positive or not

    • Patients with cytologically positive pleural or pericardial fluid, regardless of the appearance on plain x-ray
       
  • Measurable disease, defined as at least one unidimensionally measurable lesion ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan

Prior/Concurrent Therapy:

  • Patients may have received one and only one course of chemotherapy prior to enrolling on CALGB 30610, which must have included cisplatin and etoposide
    • If a patient has had one course of cisplatin/etoposide prior to registration, the patient must have had all of the prior-to-registration tests prior to starting their first course of chemotherapy

    • Registration to CALGB-30610 must take place within 14-21 days after the start of the non-protocol therapy; failing to do all of the above will make the patient NOT eligible for CALGB-30610
  • No prior radiotherapy or chemotherapy (except for the chemotherapy described above) for SCLC

  • No prior mediastinal or thoracic radiotherapy

  • No prior complete surgical resection of SCLC

  • No concurrent treatment with hormones or other chemotherapeutic agents except for steroids given for adrenal failure; hormones administered for non-disease-related conditions (e.g., insulin for diabetes); and intermittent use of dexamethasone as an antiemetic

Patient Characteristics:

  • ECOG performance status 0-2

  • Granulocytes ≥ 1,500/mm³

  • Platelet count ≥ 100,000/mm³

  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

  • AST ≤ 2.0 times ULN

  • Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 70 mL/min

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception

OBJECTIVES:

Primary

  1. To determine whether administering high-dose thoracic radiotherapy, 70 Gy (2 Gy once daily over 7 weeks) or 61.2 Gy (1.8 Gy once daily for 16 days followed by 1.8 Gy twice daily for 9 days), will improve median and 2-year survival compared with 45 Gy (1.5 Gy twice daily over 3 weeks) in patients with limited-stage small cell lung cancer.

Secondary

  1. To compare treatment-related toxic effects of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer.

  2. To compare response rates, failure-free survival, and toxicity of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer.

  3. To compare rates of local relapse, distant metastases, and brain metastases with these regimens.

  4. To describe the patterns of use of thoracic intensity-modulated radiotherapy (IMRT) in patients with limited-stage small cell lung cancer.

OUTCOMES

Primary Outcome(s)

Overall survival time between 3 treatment arms

Secondary Outcome(s)

  • Toxicity

  • Complete and partial response rates

  • Failure-free survival

  • Local tumor progression according to RECIST criteria

  • Rates of distant metastases and intracranial metastases

National Enrollment to Date: 337/729

Back to top

ECOG 5508: “Randomized Phase III Study of Maintenance Therapy with Bevacizumab, Pemetrexed or Both Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Stage Non-Squamous Non-Small Cell Lung Cancer”

OUTLINE:
This is a randomized, multicenter study. Patients are stratified according to gender (male vs. female), stage of disease (IIIB-T4Nx [with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation] and IV M1a vs. IV M1b vs. recurrent), best response to first-time therapy (complete response/partial response vs. stable disease), and smoking status (never vs. smoker).

  • Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration.
  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1.
  • Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1.
  • Arm III: Patients receive bevacizumab as in arm I and pemetrexed as in arm II. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

-Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics, protein biomarkers, proteomic profiling (closed as of 04/01/10), and other analyses.

-After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.

ELIGIBILITY:

DISEASE CHARACTERISTICS:

  • Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)
  • Predominant non-squamous histology
  • NSCLC not otherwise specified allowed
  • Mixed tumors are categorized by the predominant cell type
  • Must meet 1 of the following criteria:
  • Stage IV disease including M1a or M1b stages or recurrent disease
  • Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy
  • Measurable or non-measurable disease as defined by RECIST criteria
  • Patient must have an overall stable or better response after 4 courses of induction therapy
  • No cavitary lesions in the lungs
  • Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Leukocytes ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin ≤ institutional upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min
  • Urine protein: urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy
  • No prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ

  • No major hemoptysis within the past 4 weeks
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Serious cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet
  • No history of arterial thrombotic events or major bleeding within the past 12 months
  • No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
  • No significant traumatic injury in the past 3 months
  • No clinically significant cardiovascular disease
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No history of serious non-healing wounds, ulcers, or bone fractures

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 12 months since prior adjuvant chemotherapy
  • At least 2 weeks since prior radiotherapy
  • Patients must not have had any major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration
  • Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol
  • More than 7 days since a core biopsy
  • No prior systemic chemotherapy for advanced stage lung cancer
  • No prior paclitaxel, pemetrexed disodium, or bevacizumab
  • Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy
  • No concurrent anti-retroviral therapy in patients with HIV infection

OBJECTIVES:

Primary

  • To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs. pemetrexed disodium vs. bevacizumab and pemetrexed disodium following induction therapy.

Secondary

  • To determine the response rate in patients treated with these regimens.
  • To evaluate the progression-free survival (PFS) of patients treated with these regimens.
  • To define the toxicity of these regimens in these patients.
  • To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate.
  • To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity.
  • To determine the frequency of TSER*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium.
  • To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response.
  • To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes.
  • To explore the association between proteomic profiles and ICAM, VEGF, and FGF-beta with the clinical outcomes of the study (OS, PFS, and response) (Closed as of 04/01/2010).
  • To evaluate the ability of FOX03a to predict first-line treatment outcome in non-squamous NSCLC.(Closed as of 04/01/2010)
  • To evaluate the ability of ADSS1 to predict outcome of pemetrexed maintenance treatment in non-squamous NSCLC.(Closed as of 04/01/2010)
  • To develop proteomic classifiers to identify patient populations that would benefit from bevacizumab or pemetrexed therapy.(Closed as of 04/01/2010)

National Enrollment to Date:  843/1282

Back to top