Clinical Trial 17908

Cancer Type: Thoracic
Interventions:750009 (Rilotumumab); 765338 (AZD4547); 772256 (Palbociclib); AMG102 (Rilotumumab); AZD4547; BMN-673 (Talazoparib); BMS-936558 (Nivolumab); Dexamethasone; Erlotinib; GDC-0032 (Taselisib); Ipilimumab; MEDI4736 (Durvalumab); Nivolumab; Palbociclib; Rilotumumab; Talazoparib; Tarceva (Erlotinib); Taxotere (docetaxel); Yervoy (Ipilimumab); docetaxel

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:

  • Jhanelle Gray

Overview

Study Title

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

Summary

The purpose of the treatment part of this study is to compare the effects, good and bad, of these investigational agents to the usual approach to treating this type of cancer.

Objective

Primary Objective of the Master Protocol: The overarching goal for this protocol is to establish a National Clinical Trials Network (NCTN) mechanism for genomically screening large but homogeneous cancer populations and subsequently assigning and accruing simultaneously to a multi-substudy "Master Protocol". Biomarker-driven sub-studies in this protocol will compare new targeted therapy (TT) or targeted therapy combinations (TTC) to SOC therapy based on designated therapeutic biomarker-drug combinations, with the ultimate goal being approval of 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 (NMT) to SoC also with the goal of approval. We hypothesize that this Master Protocol mechanism will yield definable and measurable efficiencies in terms of improving genomic screening of cancer patients for clinical trial entry, and improved time lines for drug-biomarker testing allowing for inclusion of the maximum numbers of otherwise eligible patients in comparison with currently employed "single screen-single trial" approaches. 1.2 Primary Objective of Each Sub-Study: a. Phase II Component - The Primary Objective within the Phase II component of each biomarker-driven sub-study is to evaluate if there is sufficient evidence to continue to the Phase III component of the sub-study by comparing investigator-assessed PFS between targeted therapy (TT) or targeted therapy combinations (TTC) versus SOC in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung. The primary objective within the Phase II component of the non-match sub-study is to evaluate if there is sufficient evidence to continue to the Phase III component of the sub-study by comparing investigator-assessed PFS between the non-match therapy (NMT) versus SOC in patients with advanced stage refractory SCCA of the lung. b. Phase III Component - The Primary Objectives of the Phase III component of each biomarker-driven substudy are: To determine if there is both a statistically and clinically-meaningful difference in investigator-assessed PFS among advanced stage refractory SCCA of the lung randomized to receive TT/TTC versus SoC. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to TT/TTC versus SoC. The Primary Objectives of the Phase III component of the non-match sub-study: To determine if there is both a statistically and clinically-meaningful difference in investigator-assessed PFS among advanced stage refractory SCCA of the lung randomized to receive NMT versus SoC. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to NMT versus SoC. Secondary Objectives of Each Sub-Study can be found in the protocol listed under the "Objectives" section.

Inclusion Criteria

  • Screening Registration:
  • Pathologically proven squamous cell cell carcinoma (SCCA) cancer of the lung confirmed by tumor biopsy and/or fine-needle aspiration; disease must be stage IV SCCA, or recurrent.
  • Progressed after receiving exactly one front-line platinum containing metastatic chemotherapy regimen
  • Adequate tumor tissue available
  • Zubrod performance status 0-1, 28 days prior to screening registration
  • Provide prior smoking history
  • Women/men of reproductive potential must have agreed to use effective contraceptive method.
  • Sub-study Assignment:
  • Measurable disease, documented by computed tomography (CT) or magnetic resonance imaging (MRI); CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless of diagnostic quality; if patient has measurable disease it must assessed within 28 days prior to sub-study treatment arm 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 registration
  • CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to randomization; must not have leptomeningeal disease, spinal cord compression or brain metastases unless: metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, AND have no residual neurological dysfunction and has been off corticosteroids at least 1 day prior to randomization
  • Fully recovered from effects of prior surgery at least 14 days prior to sub-study registration
  • Within 28 days prior to randomization: Absolute neutrophil count (ANC) >= 1,500/mcl; Platelet count >= 100,000 mcl; Hemoglobin >= 9 g/dL; Serum bilirubin equal to or less than 2 X institutional upper limit of normal (IULN); Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transferase (SGPT) (alanine aminotransferase [ALT]) within study guidelines
  • Serum creatinine equal to or less than the IULN OR measured or calculated creatinine clearance >= 50 mL/min; Zubrod performance status 0 -1 within 28 days prior to randomization
  • Pre-study history and physical within 28 days prior to randomization
  • Additional Criteria may apply

  • Exclusion Criteria

  • Sub-study:
  • EGFR mutation or anaplastic lymphoma kinase fusion; presence of EGFR mutation or ALK fusion, not eligible for sub-studies
  • Biomarker profiling results: presence of EGFR mutation/echinoderm microtubule-associated protein-like 4/ALK fusion
  • Planned concurrent chemotherapy/immunotherapy/biologic/hormonal therapy for cancer treatment (hormones for non-cancer-related conditions acceptable)
  • Grade III/IV cardiac disease; Acute hepatitis; Active/uncontrolled infection
  • History: HIV seropositivity
  • Prior malignancy except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer (in complete remission), other cancer if disease free for 5 years
  • Pregnant or nursing
  • Additional criteria may apply