Clinical Trial: NCT02154490 - My Cancer Genome

NCT02154490

Description:

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.

Related Conditions:

Squamous Cell Lung Carcinoma

Recruiting Status:

Active, not recruiting

URL:

https://clinicaltrials.gov/show/NCT02154490

Trial Eligibility

Document

Title

Brief Title: 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)

Clinical Trial IDs

ORG STUDY ID: S1400
SECONDARY ID: NCI-2014-00627
SECONDARY ID: S1400A
SECONDARY ID: S1400E
SECONDARY ID: S1400I
SECONDARY ID: S1400C
SECONDARY ID: S1400
SECONDARY ID: S1400D
SECONDARY ID: S1400B
SECONDARY ID: S1400
SECONDARY ID: S1400
SECONDARY ID: U10CA180888
NCT ID: NCT02154490

Conditions

Recurrent Squamous Cell Lung Carcinoma
Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

Drug	Synonyms	Arms
Docetaxel	Docecad, RP56976, Taxotere, Taxotere Injection Concentrate	S1400A Arm II (CLOSED TO ACCRUAL 4/2015)
Durvalumab	Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736	S1400A Arm I (MEDI4736) (CLOSED TO ACCRUAL 12/2015)
Erlotinib Hydrochloride	Cp-358,774, OSI-774, Tarceva	S1400E Arm I (CLOSED TO ACCRUAL 11/2014)
FGFR Inhibitor AZD4547	AZD4547	S1400D Arm I (AZD4547) (CLOSED TO ACCRUAL 04/12/2017)
Ipilimumab	Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy	S1400I Arm I (nivolumab, ipilimumab)
Nivolumab	BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo	S1400I Arm I (nivolumab, ipilimumab)
Palbociclib	Ibrance, PD-0332991, PD-332991	S1400C Arm I (palbociclib)
Rilotumumab	AMG 102, Anti-HGF Monoclonal Antibody AMG 102, Fully Human Anti-HGF Monoclonal Antibody AMG 102	S1400E Arm I (CLOSED TO ACCRUAL 11/2014)
Talazoparib	BMN 673, BMN-673	S1400G (talazoparib)
Taselisib	GDC-0032	S1400B Arm I (taselisib) (CLOSED TO ACCRUAL 12/12/2016)
Tremelimumab	Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, ticilimumab	S1400F (durvalumab, tremelimumab)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      Screening component:

      I. 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.? II. 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:

      III. 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) IV. 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) V. 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):

      VI. To evaluate the objective response rate (confirmed and unconfirmed, complete and
      partial). (Phase II) VII. 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 #1: Phase II/III Design:

      I. To compare response rates (confirmed and unconfirmed, complete and partial responses)
      among patients randomized to receive investigational therapy versus SoC. (Phase II) II. To
      evaluate the frequency and severity of toxicities associated with investigational therapy
      versus SoC. (Phase II) III. 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 Tumors (RECIST) (1.1). (Phase II) III. To compare the response rates (confirmed and
      unconfirmed, complete and partial) among patients randomized to receive investigational
      therapy versus SoC. (Phase III) IV. 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):

      V. To evaluate PFS and OS with investigational therapy. (Phase II) VI. To evaluate the DoR
      among patients who achieve a CR or PR (confirmed and unconfirmed) by RECIST 1.1. (Phase II)
      VII. To evaluate the frequency and severity of toxicities associated with investigational
      therapy. (Phase II) VIII. To compare the response rates (confirmed and unconfirmed, complete
      and partial) among patients randomized to receive investigational therapy versus SoC. (Phase
      III) IX. To evaluate the frequency and severity of toxicities associated with investigational
      therapy versus SoC. (Phase III)

      TERTIARY OBJECTIVES:

      I. 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) II. To identify
      additional predictive tumor/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.

      III. To evaluate potentially predictive biomarkers for non-match therapy (NMT) in the
      non-match studies.

      IV. To identify potential resistance biomarkers at disease progression. V. 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 12/18/2015) Patients with tumors 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 12/18/2015) 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 (CLOSED TO ACCRUAL 12/12/2016): Patients with tumors 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 (CLOSED TO ACCRUAL 09/01/2016): Patients with tumors 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 (CLOSED TO ACCRUAL 10/31/2016): Patients with tumors 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 11/25/2014): Patients with tumors 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.

      S1400F: Patients with disease progression during or after prior anti-PD-1 or anti-PD-L1
      antibody monotherapy as their most recent line of treatment receive durvalumab (IV over 60
      minutes) and tremelimumab (IV over 60 minutes) on day 1 for courses 1-4 and durvalumab IV
      alone on day 1 of course 5 and subsequent courses until disease progression or unacceptable
      toxicity. Courses repeat every 28 days.

      S1400G: Patients with tumors positive for homologous recombination repair deficiency receive
      talazoparib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease
      progression or unacceptable toxicity.

      S1400I: Patients with tumors 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.

Trial Arms

Name	Description	Interventions
S1400A Arm I (MEDI4736) (CLOSED TO ACCRUAL 12/2015)	Patients with tumors that do not match one of the currently active drug-biomarker combinations randomized to Arm I receive anti-B7H1 monoclonal antibody MEDI4736 IV over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.	Durvalumab
S1400A Arm II (CLOSED TO ACCRUAL 4/2015)	Patients with tumors that do not match one of the currently active drug-biomarker combinations randomized to Arm II 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)	Docetaxel
S1400A Arm III (MEDI4736)	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 registered to Arm III receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.	Durvalumab
S1400B Arm I (taselisib) (CLOSED TO ACCRUAL 12/12/2016)	Patients with tumors positive for PI3KCA randomized to Arm I receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Taselisib
S1400B Arm II (CLOSED TO ACCRUAL 12/18/2015)	Patients with tumors positive for PI3KCA randomized to Arm II 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)	Docetaxel
S1400B Arm III (taselisib) (CLOSED TO ACCRUAL 12/12/2016)	Re-Registration Treatment with GDC-0032 (Taselisib). Upon progression patients in Arm 2 may be eligible for Re-Registration to receive GDC-0032. Patients will receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Taselisib
S1400C Arm I (palbociclib)	Patients with tumors positive for CDK4/6, CCND1, CCND2, and CCND3 randomized to Arm I receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Palbociclib
S1400C Arm II (CLOSED TO ACCRUAL 12/18/2015)	Patients with tumors positive for CDK4, CCND1, CCND2, and CCND3 randomized to Arm II 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)	Docetaxel
S1400C Arm III (palbociclib)	Re-Registration Treatment with palbociclib. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive palbociclib. Patients will receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Palbociclib
S1400D Arm I (AZD4547) (CLOSED TO ACCRUAL 04/12/2017)	Patients with tumors positive for FGFR1, FGFR2, and FGFR3 randomized to Arm I receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	FGFR Inhibitor AZD4547
S1400D Arm II (CLOSED TO ACCRUAL 10/31/2016)	Patients with tumors positive for FGFR1, FGFR2, and FGFR3 randomized to Arm II 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)	Docetaxel
S1400D Arm III (AZD4547) (CLOSED TO ACCRUAL 10/31/2016)	Re-Registration Treatment with AZD4547. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive AZD4547. Patients will receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	FGFR Inhibitor AZD4547
S1400E Arm I (CLOSED TO ACCRUAL 11/2014)	Patients with tumors positive for HGF/c-MET randomized to Arm I receive rilotumumab IV on day 1 and erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (permanently closed to accrual on 11/25/14)	Erlotinib Hydrochloride Rilotumumab
S1400E Arm II (CLOSED TO ACCRUAL 11/2014)	Patients with tumors positive for HGF/c-MET randomized to Arm II receive erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (permanently closed to accrual on 11/25/14)	Erlotinib Hydrochloride
S1400F (durvalumab, tremelimumab)	Patients with disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment receive durvalumab (IV over 60 minutes) and tremelimumab (IV over 60 minutes) on day 1 for courses 1-4 and durvalumab IV alone on day 1 of course 5 and subsequent courses until disease progression or unacceptable toxicity. Courses repeat every 28 days.	Durvalumab Tremelimumab
S1400G (talazoparib)	Patients with tumors positive for homologous recombination repair deficiency receive talazoparib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Talazoparib
S1400I Arm I (nivolumab, ipilimumab)	Patients with tumors 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 randomized to Arm I receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third cycle. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Ipilimumab Nivolumab
S1400I Arm II (nivolumab)	Patients with tumors 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 randomized to Arm II receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  SCREENING/PRE-SCREENING REGISTRATION:

          -  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, or recurrent; the primary diagnosis of SCCA should be established using the
             current World Health Organization (WHO)/International Association for the Study of
             Lung Cancer (IASLC)-classification of Thoracic Malignancies; the diagnosis is based on
             hematoxylin and eosin (H&E) stained slides with or without specific defined
             immunohistochemistry (IHC) characteristic (p40/p63 positive, transcription termination
             factor [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:

               -  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)

               -  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 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 mm^3 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 Clinical Laboratory Improvement Act (CLIA) biomarker
                  profiling; 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 deoxyribonucleic acid (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 epidermal growth factor receptor (EGFR) mutation or
             anaplastic lymphoma kinase (ALK) fusion; EGFR/ALK testing is not required prior to
             registration and is included in the Foundation Medicine Incorporated (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 also be offered participation in banking for future use of specimens

          -  Patients must be willing to provide prior smoking history as required on the S1400
             Onstudy Form

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system

          -  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

          -  SUB-STUDY REGISTRATION:

          -  Patients whose biomarker profiling results indicate the presence of an EGFR mutation
             or echinoderm microtubule-associated protein-like 4 (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 computed tomography (CT) or
             magnetic resonance imaging (MRI); the CT from a combined positron emission tomography
             (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 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 central nervous
             system (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 24 hours prior to sub-study registration

          -  Patient must have fully recovered from the effects of prior 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

          -  Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to
             sub-study registration

          -  Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study registration

          -  Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study registration

          -  Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to
             sub-study registration; for patients with liver metastases, bilirubin must be =< 5 x
             IULN

          -  Either alanine aminotransferase (ALT) or aspartate aminotransferase (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, either ALT or AST must be =< 5
             x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

          -  Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50
             mL/min using the following Cockcroft-Gault Formula within 28 days prior to sub-study
             registration

          -  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

          -  Patients with a known history of human immunodeficiency virus (HIV) seropositivity:

               -  Must have undetectable viral load using standard HIV assays in clinical practice

               -  Must have cluster of differentiation (CD)4 count >= 400/mcL

               -  Must not require prophylaxis for any opportunistic infections (i.e., fungal,
                  Mycobacterium avium complex [mAC], or pneumocystis jiroveci pneumonia [PCP]
                  prophylaxis)

               -  Must not be newly diagnosed within 12 months prior to sub-study registration

          -  Prestudy history and physical exam must be obtained within 28 days 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

          -  As part of the OPEN registration process the treating institution?s identity is
             provided in order to ensure that the current (within 365 days) date of institutional
             review board approval for this study has been entered into the system

          -  Patients with impaired decision-making capacity are eligible as long as their
             neurological or psychological condition does not preclude their safe participation in
             the study (e.g., tracking pill consumption and reporting adverse events to the
             investigator)

          -  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.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II)
Time Frame:	From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual
Safety Issue:
Description:	A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.

Secondary Outcome Measures

Measure:	Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.

Measure:	Frequency and severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure:	Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III)
Time Frame:	From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Safety Issue:
Description:	Descriptive data will be presented.

Measure:	Overall survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure:	Progression free survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure:	Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.

Measure:	Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Analysis of response rates will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure:	Severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure:	Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.

Details

Phase:
Primary Purpose:	Observational
Overall Status:	Active, not recruiting
Lead Sponsor:	Southwest Oncology Group

Last Updated

November 12, 2020

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