S1400 Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer

Official Title

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

Summary:

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 hybrid "Master Protocol" (S1400). 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.

Trial Description

Primary Outcome:

  • IA-PFS as defined by RECIST 1.1 (Design #1, Phase II)
  • IA-PFS in patients with advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC (Design #2, Phase III)
  • Less than 33% improvement in median IA-PFS as defined as RECIST 1.1 (Design #1, Phase III)
  • Objective Response Rate (ORR) (confirmed and unconfirmed, complete and partial) (Design #2, Phase II)
  • OS (Design #1, Phase III)
  • OS in patients with advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC (Design #2, Phase III)
Secondary Outcome:
  • DoR among patients who achieve a CR or PR by RECIST 1.1 (Design #2, Phase II)
  • Frequency and severity of toxicities associated with investigational therapy versus SoC (Design #2, Phase III)
  • IA-PFS, censoring patients with symptomatic deterioration (SD) at the time of SD (Design #1, Phase III)
  • OS with investigational therapy (Design #2, Phase II)
  • PFS with investigational therapy (Design #2, Phase II)
  • Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by RECIST 1.1 (Design #1, Phase II and III)
  • Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC (Design #2, Phase III)
  • Severity of toxicities associated with investigational therapy versus SoC (Design #2, Phase II)
  • Toxicity frequencies, monitored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Design #1, Phase II and III)
PRIMARY OBJECTIVES:
Screening component:
  • 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-sub-study "Master Protocol."
  • To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study.
Sub-study-specific Objectives:
Design #1: Phase II/III Design:
  • To evaluate if there is sufficient evidence to continue to the Phase III component of the sub-study by comparing investigator-assessed progression-free survival (IA-PFS) between investigational therapy versus standard therapy (SoC) in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung. (Phase II)
  • To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III)
  • To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III)
Design#2 Phase II followed by Phase III (Sequential Phase II to Phase III):
  • To evaluate the objective response rate (confirmed and unconfirmed, complete and partial). (Phase II)
  • To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III) VIII. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III)
SECONDARY OBJECTIVES:

Sub-study-specific Objectives: Design

Phase II/III Design:
  • To compare response rates (confirmed and unconfirmed, complete and partial responses) among patients randomized to receive investigational therapy versus SoC. (Phase II)
  • To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase II)
  • To evaluate the duration of response (DoR) among patients who achieve a complete response (CR) or a partial response (PR) by Response Evaluation Criteria In Solid Tumours (1.1). (Phase II)
  • To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III)
  • To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III)
Design #2: Phase II followed by Phase III (Sequential Phase II to Phase III):
  • To evaluate PFS and OS with investigational therapy. (Phase II)
  • To evaluate the DoR among patients who achieve a CR or PR (confirmed and unconfirmed) by Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. (Phase II)
  • To evaluate the frequency and severity of toxicities associated with investigational therapy. (Phase II)
  • To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III)
  • To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III)
TERTIARY OBJECTIVES:
  • To evaluate the treatment arm randomization acceptance rate (TARAR) within each treatment arm of each sub-study defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. (Design #1: Phase II/III Design)
  • To identify additional predictive tumour/blood biomarkers that may modify response or define resistance to the targeted therapy (TT)/targeted therapy combination (TTC) beyond the chosen biomarker for biomarker-driven sub-studies.
  •  To evaluate potentially predictive biomarkers for non-match therapy (NMT) in the non-match studies.
  • To identify potential resistance biomarkers at disease progression.
  • To establish a tissue/ blood repository from patients with refractory SCCA of the lung.
OUTLINE:
Patients are assigned to a biomarker-driven targeted therapy phase II study. If the objectives response rate observed is judged sufficient, patients proceed to a randomized phase III trial and are randomized to biomarker-driven targeted therapy or standard of care.

S1400A: (Closed to accrual 12/2015) Patients with tumours that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are assigned to Arm I. Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period (Arm III).

ARM I: (Closed to accrual 12/2015) Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 4/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #2 4/22/15)

ARM III: For patients assigned to Arm 1, MEDI4736: Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment with Arm 3, MEDI4736 for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period. Patients will only be able to restart treatment once; thus a maximum of two 12-month periods will be allowed. Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.

S1400B: Patients with tumours positive for phosphoinositide 3-kinase (PI3KCA) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, GCD-0032 after disease progression on current treatment (Arm III).

ARM I: Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015)

ARM III: Re-Registration Treatment with GDC-0032 (Taselisib) Upon progression patients in Arm 2 may be eligible for Re-Registration to receive GDC-0032. Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400C: Patients with tumours positive for cyclin dependent kinase 4 (CDK4), cyclin D1 (CCND1), cyclin D2 (CCND2), and cyclin D3 (CCND3) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, palbociclib, after disease progression on current treatment (Arm III).

ARM I: Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015)

ARM III: Re-Registration Treatment with Palbociclib. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive palbociclib. Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

S1400D: Patients with tumours positive for fibroblast growth factor receptor (FGFR) 1, FGFR2, and FGFR3 are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, AZD4547, after disease progression on current treatment (Arm III).

ARM I: Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015) ARM III: Re-Registration Treatment with AZD4547. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive AZD4547. Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400E (CLOSED TO ACCRUAL 11/2014): Patients with tumours positive for met proto-oncogene (MET) are randomized to 1 of 2 treatment arms. (permanently closed to accrual on 11/25/14)

ARM I: Patients receive rilotumumab IV on day 1 and erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400I: Patients with tumours that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, all patients are followed up periodically for up to 3 years from date of screening registration.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society