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SWOG 1400 (Lung Master Protocol)

A Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer

Inclusion Criteria

  • Patients must have pathologically proven squamous cell carcinoma of the lung confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV. Recurrent disease qualifies as Stage IV. Mixed histologies are not allowed.
  • Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment. Patients will either consent to the Screening consent or the Pre-Screening consent, not both. These criteria are:
    • Screening at progression on prior treatment: To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (Stages I-IV). At least one of these lines of therapy must have been a platinum based chemotherapy regimen. Patients must have progressed following the most recent line of therapy. For patients whose prior systemic therapy was for Stage I-III disease only (i.e. patient has not received any treatment for Stage IV disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy.
    • Pre-Screening prior to progression on current treatment: To be eligible for pre-screening, current treatment must be for Stage IV disease and patient must have received at least one dose of the current regimen. Patients must have previously received or currently be receiving a platinum-based chemotherapy regimen. Patients on first-line platinum-based treatment are eligible upon receiving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-study assignment until they progress and the S1400 Notice of Progression is submitted
  • Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥ 0.2 mm3 tumor volume. The local interpreting pathologist must review and sign off on the Local Pathology Review Form prior to screening/pre-screening registration. Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling. If archival tumor is exhausted, then a new fresh tumor biopsy that is formalin fixed and paraffin embedded must be obtained.
  • Patients must not have a known EGFR mutation or ALK fusion.
  • Patients must have a Zubrod performance status 0-1 documented within 28 days prior to screening or pre-screening registration.
  • Patients must be ≥ 18 years of age.
  • Patients must also be offered participation in banking for future use of specimens.
  • Patients must be willing to provide prior smoking history.

Sub-Study Registration

  • For patients screened at progression on prior treatment, a sub-study assignment should be received within 16 days of screening registration.
  • For patients pre-screened prior to progression on current therapy, submission of the Notice of Progression Form is required to receive a sub-study assignment. The sub-study assignment should be received from the SWOG Statistical Center within 1 day of submission of the form. Patients must then register to the assigned sub-study in order to receive their treatment randomization assignment.
  • Patient must meet the common eligibility criteria across all sub-studies listed in this section below as well as any additional criteria listed in the assigned sub-study protocol.
    • Patients whose biomarker profiling results indicate the presence of an EGFR mutation or EML4/ALK fusion are not eligible.
    • Patients must have progressed, in the opinion of the treating investigator, following the most recent line of therapy. 
    • Patients must not have received radiation therapy with 14 days prior to sub-study registration.
    • Patients must not have received any prior systemic chemotherapy, immunotherapy or investigational drug within 21 days prior to sub-study registration. Patients must have recovered (≤ Grade 1) from any side effects of prior therapy.
    • Patients must have measurable disease documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease prior to registration.
    • Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to sub-study registration. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 1 day prior to sub-study registration.
    • Patients must have fully recovered from the effects of surgery at least 14 days prior to sub-study registration.
    • Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
    • Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000/mcl, and hemoglobin ≥ 9 g/dL obtained within 28 days prior to sub-study registration.
    • Patients must have adequate hepatic function as defined by serum bilirubin ≤ Institutional Upper Limit of Normal (IULN) and either AST or ALT  2 x IULN within 28 days prior to sub-study randomization (if both AST and ALT are done, both must be ≤ 2 IULN). For patients with liver metastases, bilirubin and either AST or ALT must be ≤ 5 x IULN (if both ALT and AST are done, both must be ≤ 5 x IULN).
    • Patients must have a serum creatinine ≤ the IULN OR measured or calculated creatinine clearance ≥ 50 cc/min using the Cockroft-Gault Formula.
    • Patients must have Zubrod performance status 0-1.
    • Patients must not have any Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia.
    • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection.
    • Patients with a known history of HIV seropositivity must have (1) undetectable viral load using standard HIV assays in clinical practice, (2) CD4 count ≥ 400/mcL, (3) not require prophylaxis for any opportunistic infections (i.e., fungal, mAC, or PCP prophylaxis), and (4) not be newly diagnosed within 12 months prior to sub-study registration.
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage 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 five years.
    • Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.

Treatment Plan

Patients will first have fresh or archived tissue submitted for biomarker testing. Within 16 days, results will be available and eligible patients will be randomized to the appropriate sub-study, depending on the specific marker identified. If no marker is identified, patients will be offered sub-study I, which is testing nivolumab (anti-PD1 agent) + ipilimumab (anti-CTLA-4 agent) versus nivolumab alone. The target biomarker for each sub-study is noted in parentheses below. Treatment on all sub-studies continues until progression of disease, symptomatic deterioration, unacceptable toxicity, treatment delay > 28 days, or patient withdrawal for any reason. Upon progression, patients may be eligible for another sub-study, as determined by the SWOG Statistical Center.

Sub-study B (P13K) 
GDC-0032 4 mg p.o. daily

Sub-study C (CDK4/6) 
Palbociclib 125 mg p.o. daily, 21 days on, 7 days off, q28days

Sub-study D (FGFR)
AZD4547 80 mg p.o. BID

Sub-study I (Non-match Sub-study)
Arm 1 Nivolumab 3 mg/kg IV q14days + Ipilimumab 1 mg/kg IV q42days
Arm 2 Nivolumab 3 mg/kg IV q14days

All investigational study drugs (GDC-0032, Palbociclib, AZD4547, Nivolumab, and Ipilimumab) will be provided free of charge for these studies.

The biomarker testing will also be provided free of charge. If patients require a biopsy for eligibility, the cost of the biopsy will be paid for by the study.