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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT02154490
First received: May 30, 2014
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Biological: anti-B7H1 monoclonal antibody MEDI4736
Drug: PI3 kinase inhibitor GDC-0032
Drug: palbociclib isethionate
Drug: FGFR inhibitor AZD4547
Biological: rilotumumab
Drug: docetaxel
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: S1400 Phase II/III Biomarker-Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • progression free survival ( PFS ) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 (Phase II) [ Time Frame: From date of sub-study treatment arm randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] [ Designated as safety issue: No ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to PFS, comparing the two treatment arms.

  • Less than 33% improvement in median PFS as defined as RECIST 1.1 (Phase III) [ Time Frame: From date of sub-study treatment arm randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] [ Designated as safety issue: No ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to PFS, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

  • overall survival (OS) (Phase III) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to OS, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.


Secondary Outcome Measures:
  • Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by RECIST 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Toxicity frequencies, monitored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Analysis will be performed using a chi squared or Fisher's exact test, as appropriate.

  • PFS, as defined by modified immune-related response criteria (irRC) (Sub-Study A) [ Time Frame: From date of sub-study treatment arm randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Response rate, as defined by irRC (Sub-Study A) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Percentage of participants achieving response as defined by modified immune-related response criteria


Other Outcome Measures:
  • Screen success rate, monitored by the percentage of screened patients that register to a therapeutic sub-study [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Treatment arm randomization acceptance rate, monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 10000
Study Start Date: June 2014
Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: S1400A Arm I (MEDI4736)
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. Courses repeat every 2 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Upon evidence of progressive disease following discontinuation of 12 months of treatment, patients may restart treatment for up to 12 additional months.
Biological: anti-B7H1 monoclonal antibody MEDI4736
Given IV
Other Name: MEDI4736
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: S1400A Arm II (docetaxel)
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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Experimental: S1400B Arm I (GDC-0032)
Patients tumors positive for PI3KCA randomized to Arm I receive PI3 kinase inhibitor GDC-0032 PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: PI3 kinase inhibitor GDC-0032
Given PO
Other Name: GDC-0032
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: S1400B Arm II (docetaxel)
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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Experimental: S1400C Arm I (palbociclib)
Patients with tumors positive for CDK4/6, CCND1, CCND2, and CCND3 randomized to Arm I receive palbociclib isethionate PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: palbociclib isethionate
Given PO
Other Names:
  • palbociclib
  • PD 0332991-0054
  • PD-0332991
  • PF-00080665-73
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: S1400C Arm II (docetaxel)
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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Experimental: S1400D Arm I (AZD4547)
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.
Drug: FGFR inhibitor AZD4547
Given PO
Other Name: AZD4547
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: S1400D Arm II (docetaxel)
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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Experimental: S1400E Arm I (rilotumumab, erlotinib)
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.
Biological: rilotumumab
Given IV
Other Names:
  • AMG 102
  • anti-HGF monoclonal antibody AMG 102
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: S1400E Arm II (erlotinib)
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.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • SCREENING REGISTRATION:
  • Patients must have pathologically proven squamous cell non-small cell lung cancer (NSCLC) confirmed by tumor biopsy and/or fine-needle aspiration; disease must be either advanced, incurable stage IIIB or stage IV NSCLC; 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 will be allowed provided that they contain >= 50% of the squamous component
  • Patients must have progressed after receiving exactly one front-line platinum containing metastatic chemotherapy regimen
  • Patients must have adequate tumor tissue available (defined as >= 20% tumor cells as confirmed by the treating institution's local pathologist); patients must agree to have this tissue submitted to Foundation Medicine for common broad platform Clinical Laboratory Improvement Amendments (CLIA) biomarker profiling; if archival tumor is used either a tumor block or at a minimum 12 formalin-fixed paraffin-embedded (FFPE) slides 4-5 microns thick are required, but 20 slides are strongly recommended; in the event that patient's archival tumor material is derived from a fine needle aspirate and the tumor material from fine needle aspirate or from core needle biopsy is exhausted a new fresh tumor biopsy will be obtained and will be formalin fixed and paraffin-embedded
  • Patients must not have a known epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion; in addition, patients whose biomarker profiling results indicate the presence of an EGFR mutation or ALK fusion will be notified that they are not eligible for any of the sub-studies
  • Patients must have Zubrod performance status =< 2 documented within 28 days prior to screening registration
  • Patients must also be offered participation in banking for future use of specimens
  • Patients must be willing to provide prior smoking history
  • Patients or their legally authorized representative 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
  • 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
  • SUB-STUDY ASSIGNMENT:
  • 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 be registered to the assigned sub-study within 28 calendar days of receiving sub-study assignment from the statistical center
  • 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; 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; all disease must be assessed and documented on the Baseline Tumor Assessment Form; patients with active new disease growth in previously irradiated site are eligible
  • 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 treatment arm randomization; 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 28 days following treatment, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 14 days prior to randomization
  • Patients must have progressed after receiving exactly one front-line platinum containing metastatic chemotherapy regimen; patients must not have received any prior systemic chemotherapy or investigational drug within 21 days prior to sub-study treatment arm randomization; patients must have recovered (=< grade 1) from any side effects of prior therapy; localized palliative radiotherapy >= 14 days is allowed
  • Patient must have fully recovered from the effects of prior surgery prior to sub-study treatment arm randomization
  • 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 treatment arm randomization
  • Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study treatment arm randomization
  • Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study treatment arm randomization
  • Serum bilirubin =< 2 X institutional upper limit of normal (IULN) within 28 days prior to sub-study treatment arm randomization
  • Either serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transferase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN within 28 days prior to sub-study treatment arm randomization (if both SGOT and SGPT are done, both must be =< 2 IULN)
  • For patients with liver metastases, bilirubin and either SGOT and SGPT must be =< 5 x IULN
  • Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 cc/min using the following Cockroft-Gault Formula within 28 days prior to sub-study treatment arm randomization
  • Patients must have Zubrod performance status =< 2 documented within 28 days prior to sub-study treatment arm randomization
  • 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 must not have a known history of human immunodeficiency virus (HIV) seropositivity
  • Prestudy history and physical must be obtained within 28 days prior to sub-study treatment arm randomization
  • 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
  • S1400A:
  • Patients must not have any prior exposure to immunotherapy such as, but not limited to other anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death (PD)-1, or anti-PD-L1 antibodies excluding vaccines within 28 days prior to sub-study treatment arm randomization
  • Patients must not have received or be planning to receive any anti-cancer therapy whether chemotherapy, or biologic therapy, therefore receipt of the last dose of anti-cancer therapy, (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization) > 21 days prior to randomization (> 14 days prior to randomization for patients who have received prior TKIs [e.g. erlotinib, gefitinib, or crizotinib] and > 42 days for nitrosoureas or mitomycin-c)
  • 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 (eg, insulin for diabetes and hormone replacement therapy) is acceptable; patients must not have received or be planning to receive any immunosuppressive medication within 28 days prior to sub-study treatment arm randomization, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
  • Patients must not have any active or prior documented autoimmune or inflammatory disease (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome) within 3 years prior to sub-study treatment arm randomization; patients with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded
  • Patients must not have any history of primary immunodeficiency
  • Patients must not have any prior grade >= 3 immune-related adverse event (irAE) or any unresolved irAE > grade 1
  • Patients must not have any history of organ transplant that requires use of immunosuppressives
  • Patients must not have any known allergy or reaction to any component of the MEDI4736 formulation
  • Patients must not have a known history of tuberculosis
  • Patients must not have received a live attenuated vaccination within 28 days prior to sub-study treatment arm randomization
  • Patients must not have known HIV, hepatitis B or C positivity
  • S1400B:
  • Hemoglobin A1c (HbA1c) < 7% obtained within 28 days prior to sub-study treatment arm randomization
  • Fasting glucose < 125 mg/dl obtained within 28 days prior to sub-study treatment arm randomization
  • Patients must not have Type 1 or 2 diabetes which requires insulin
  • Patients must not have active or a history of small or large intestine inflammation such as Crohn's disease or ulcerative colitis
  • Patients must not require daily supplemental oxygen
  • Patients must be able to take oral medications; patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of GDC-0032 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days post the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate cytochrome p450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates
  • Patients must not have received prior treatment of docetaxel as part of frontline platinum-containing chemotherapy (S1400B)
  • S1400C:
  • Patients must not be taking within 7 days prior to sub-study treatment arm randomization, nor plan to take while on protocol treatment, CYP3A4 inhibitors and/or strong CYP3A4 inducers; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
  • Patients must not be taking within 7 days prior to sub-study treatment arm randomization, nor plan to take while on protocol treatment drugs that are known to prolong the QT interval
  • Patients must not have QTc > 480msec (based on the mean value of the triplicate electrocardiograms [ECGs]), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
  • Patients must not have uncontrolled electrolyte disorders which can compound the effects of a QTc-prolonging drug (eg, hypocalcemia, hypokalemia, hypomagnesemia)
  • Patients must be able to take oral medications; patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of palbociclib (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients must not have received prior treatment of docetaxel as part of frontline platinum-containing chemotherapy (S1400C)
  • S1400D:
  • Patients must be >= 25 years of age (skeleton maturation is complete)
  • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days after the last dose of study treatment drugs, herbal supplements and/or foods known to modulate CYP3A4 or cytochrome p450, family 2, subfamily D, polypeptide 6 (CYP2D6) enzyme activity and drugs that are known to be CYP3A4 substrates
  • Patients must not have received Nitrosourea or mitomycin C within 42 days prior to sub-study treatment arm randomization
  • Patients must not have had any prior exposure to any agent with FGFR inhibition as its primary pharmacology
  • Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); nor any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
  • Patients must be able to take oral medications; patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of AZD4547 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients must not have a history of hypersensitivity to active or inactive excipients of AZD4547 or drugs with a similar chemical structure or class to AZD4547
  • Patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02154490

Contacts
Contact: Crystal Miwa 210-614-8808 ext 1019 cmiwa@swog.org
Contact: Dana Sparks, MAT 210-614-8808 ext 1004 dsparks@swog.org

  Show 304 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Vassiliki Papadimitrakopoulou Southwest Oncology Group
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02154490     History of Changes
Other Study ID Numbers: S1400, NCI-2014-00627, S1400E, S1400A, S1400C, S1400D, S1400B, S1400, S1400, U10CA180888, Lung-MAP
Study First Received: May 30, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Lung Diseases
Bronchial Neoplasms
Carcinoma, Bronchogenic
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Antibodies, Monoclonal
Docetaxel
Erlotinib
Immunoglobulins
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014