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S1400:

Phase II/III Biomarker-Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer

Objective

Overview

This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study "Master Protocol." The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes a "non-match" sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of care also with the goal of approval.

Key Inclusion Criteria

  • Patients must have pathologically proven squamous cell carcinoma (SCCA) cancer of the lung confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV SCCA as defined in Section 4.0, or recurrent. The primary diagnosis of SCCA should be established using the current WHO/IASLC classification of Thoracic Malignancies. The diagnosis is based on H&E stained slides with or without specific defined IHC characteristic (p40/p63 positive, TTF1 negative) if required for diagnosis. 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:
    1. 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) and must have progressed during or following their 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 or recurrent disease), the prior systemic therapy must have been a platinum-based chemotherapy regimen and disease progression on the platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy. For patients whose prior therapy was for Stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or checkpoint inhibitor therapy (e.g. Nivolumab or Pembrolizumab).
    2. Pre-Screening prior to progression on current treatment: To be eligible for pre-screening, current treatment must be for Stage IV or recurrent 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 or checkpoint inhibitor therapy (e.g. Nivolumab or Pembrolizumab). Patients on first-line 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 the specimen.
    • The pathologist must sign the S1400 Local Pathology Review Form confirming tissue adequacy prior to screening/pre-screening registration.
    Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling and c-Met IHC (see Section 15.1). If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12 unstained slides plus an H&E stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment.

    Patients must agree to have any tissue that remains after NGS testing retained for the use of the Translational Medicine (TM) studies (if such TM studies are defined) within any sub-study the patient is enrolled in.
  • Patients must not have a known EGFR mutation or ALK fusion. EGFR/ALK testing is not required prior to registration and is included in the FMI testing for screening/prescreening.
  • Patients must have Zubrod performance status 0-1 documented within 28 days prior to screening/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.

  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

  • COMMON ELIGIBILITY FOR ALL SUB-STUDIES:

  • 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 any prior systemic therapy (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 not have received any radiation therapy within 14 days prior to sub-study registration.

  • Patients must have measurable disease documented by CT or MRI. The CT from a combined PET/CT may be used to document only nonmeasurable disease unless it is of diagnostic quality as defined in Section 10.1c. Measurable disease must be assessed within 28 days prior to sub-study registration. 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 on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) 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 prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration.

  • Patient 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 ALT or AST ≤ 2 x IULN within 28 days prior to sub-study registration (if both ALT and AST are done, both must be < 2 IULN). For patients with liver metastases, bilirubin and either ALT or AST 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 mL/min using the Cockroft-Gault Formula.

  • Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration.

  • 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.

Phase: I/II

Learn More

IRB Protocol Number
S1400:

Clinical Trial Categories

  • Precision Medicine- Rare Tumors

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