Lung-MAP: Durvalumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers

Study Overview
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Brief Summary
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This phase II trial studies how well durvalumab works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a non-match sub-study that includes all screened patients not eligible for a biomarker-driven sub-study. Monoclonal antibodies, such as durvalumab, may be able to shrink tumors. Durvalumab may be effective in treating patients with squamous cell lung cancer.

Detailed Description
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CO-PRIMARY OBJECTIVES: I. To assess the response rate (confirmed and unconfirmed, complete and partial) among patients treated with durvalumab (MEDI4736). II. To assess the response rate (confirmed and unconfirmed, complete and partial) among programmed death ligand 1 (PD-L1) positive patients treated with MEDI4736. SECONDARY AND EXPLORATORY OBJECTIVES: I. To assess investigator-assessed progression-free survival (IA-PFS) among patients treated with MEDI4736. II. To assess IA-PFS among PD-L1 positive patients treated with MEDI4736. III. To assess overall survival (OS) in patients treated with MEDI4736. IV. To assess overall survival (OS) in PD-L1 positive patients treated with MEDI4736. V. To evaluate the frequency and severity of toxicities associated with MEDI4736. VI. To assess immune-related IA-PFS using a modified response criteria adapted for immunotherapy (immune-related response criteria [irRC]-IA-PFS) in all patients and in the subset of patients determined to be PD-L1 positive treated with MEDI4736. VII. To compare IA-PFS, irRC-IA-PFS, OS, toxicity and response rates between patients randomized to MEDI4736 versus docetaxel. TRANSLATIONAL MEDICINE OBJECTIVES: I. To identify additional predictive or prognostic tumor/blood biomarkers beyond the chosen biomarker. II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/blood repository from patients with refractory squamous cell cancer. MEDI4736 RE-TREATMENT OBJECTIVES: I. To evaluate response rates (confirmed and unconfirmed, complete and partial responses) among patients re-treated with MEDI4736. II. To estimate median PFS from the date of re-treatment. OUTLINE (CLOSED TO ACCRUAL 12/18/2015): Patients with tumors that do not match one of the currently active drug-biomarker combinations receive durvalumab intravenously (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 progression following discontinuation of 12 months of treatment, patients may restart treatment and continue for up to 12 additional months (Arm III). ARM I: (Closed to accrual 12/2015) Patients receive durvalumab 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 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. After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Official Title
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A Phase II Study of MEDI4736 for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers (Lung-Map Sub-Study)

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

Intervention / Treatment
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* Drug: Docetaxel
* Biological: Durvalumab
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) Patients must have been assigned to S1400A Patients must not have any prior exposure to immunotherapy such as, but not limited to anti-programmed death 1 (PD-1) or anti-PD-L1 antibodies; prior exposure to the following is allowed: anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, live attenuated vaccines, anti-EGFR agents and sargramostim (GM-GSF) Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to sub-study registration 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; Wegener syndrome; Hashimoto syndrome) within 3 years prior to sub-study registration; patients with vitiligo, alopecia, Grave's disease, or psoriasis requiring systemic treatment within the past 3 years are not eligible Patients must not have any history of primary immunodeficiency Patients must not have received any immunosuppressive medication within 28 days prior to sub-study registration and must not be planning to receive any such agents while on protocol treatment; however, intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent are allowed 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 registration Patients must not have known human immunodeficiency virus (HIV), hepatitis B or C positivity Patients must also be offered participation in banking for future use of specimens STEP 2 TO MEDI4736 RE-TREATMENT REGISTRATION: Patient must have progressed following 12 months of treatment with MEDI4736; patients who discontinue MEDI4736 prior to the completion of 12 months (for any reason) are not eligible; patients who have already completed two 12-month periods of treatment are not eligible Patients may have measurable or non-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 re-treatment 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 re-treatment 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 RE-TREATMENT 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 RE-TREATMENT registration; patient 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 prior to RE-TREATMENT registration, AND patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to RE-TREATMENT registration Patients must not have received any treatment after discontinuing MEDI4736 with the following exceptions; localized palliative radiation therapy is allowed for symptom management, provided and treatment is completed >= 14 days prior to RE-TREATMENT registration; local treatment for brain metastases is allowed Patients must not have received any immunosuppressive medication within 28 days prior to RE-TREATMENT registration and must not be planning to receive any such agents while on protocol treatment; however, intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent are allowed Patients must not have any prior grade >= 3 immune-related adverse event (irAE) or any unresolved irAE > grade 1 (MEDI4736 RE-TREATMENT) Patients must not have received a live attenuated vaccination within 28 days prior to RE-TREATMENT registration Patients must not have known HIV, hepatitis B or hepatitis C positivity 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 RE-TREATMENT registration Platelet count >= 100,000 mcl obtained within 28 days prior to RE-TREATMENT registration Hemoglobin >= 9 g/dL obtained within 28 days prior to RE-TREATMENT registration Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to RE-TREATMENT 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 RE-TREATMENT 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) Patients must have a serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula Patients must have Zubrod performance status of 0-1 documented within 28 days prior to RE-TREATMENT registration Prestudy history and physical exam must be obtained within 28 days prior to RE-TREATMENT registration 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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (MEDI4736 - closed to accrual 12/2015)<br>Patients 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. | Biological: Durvalumab<br>* Given IV<br>* Other names: MEDI4736;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
| Active Comparator: Arm II (docetaxel - closed to accrual 4/2015)<br>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) | Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
| Experimental: Arm III (MEDI4736 retreatment)<br>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 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. | Biological: Durvalumab<br>* Given IV<br>* Other names: MEDI4736;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate in MEDI4736-treated Participants | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Up to 3 years post registration | 
| Overall Response Rate Among PD-L1 Positive Participants Treated With MEDI4736 | The percentage of PD-L1 positive participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Up to 3 years post registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed Progression-free Survival in Participants Treated With MEDI4736 | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions or an absolute increase of >= 0.5cm, or a measurable increase in a non-target lesion, or the appearance of new lesions or death due to disease without prior documentation of progression or symptomatic deterioration. | Up to 3 years post registration | 
| Investigator-assessed Progression-free Survival in PD-L1 Positive Participants Treated With MEDI4736 | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions or an absolute increase of >= 0.5cm, or a measurable increase in a non-target lesion, or the appearance of new lesions or death due to disease without prior documentation of progression or symptomatic deterioration. | up to 3 years post registration | 
| Overall Survival in MEDI4736-treated Participants | Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. | Up to 3 years post-registration | 
| Overall Survival in PD-L1 Positive MEDI4736-treated Participants | Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. | up to 3 years post registration | 
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adverse Events (AEs) are reported by CTCAE Version 5.0 for serious adverse events only and CTCAE Version 4.0 for routine toxicity reporting. Only adverse events that are possibly, probably or definitely related to study drug are reported. | Duration of treatment and follow up until death or 3 years post registration | 
| Investigator-assessed Progression-free Survival Assessed Using a Modified Response Criteria Adapted for Immunotherapy in Participants Treated With MEDI4736 | Duration from date of sub-study registration to date of first documentation of immune related response criteria-progression assessed by local review or symptomatic deterioration (as defined above), or death due to any cause | up to 3 years post registration | 
| Investigator-assessed Progression-free Survival Assessed Using a Modified Response Criteria Adapted for Immunotherapy in PD-L1 Positive Participants Treated With MEDI4736 | Duration from date of sub-study registration to date of first documentation of immune related response criteria-progression assessed by local review or symptomatic deterioration (as defined above), or death due to any cause | up to 3 years post registration | 
| Overall Survival | Duration from date of sub-study registration (or date of screening/pre-screening registration if participant never enrolls in a sub-study) to date of death due to any cause. Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed. | Up to 3 years post registration | 
| Investigator-assessed Progression-free Survival | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration, or death due to any cause. Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed. | Up to 3 years post registration | 
| Investigator-assessed Progression-free Survival Assessed Using a Modified Response Criteria Adapted for Immunotherapy | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration, or death due to any cause. | Up to 3 years post registration | 
| Response Rate | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 or docetaxel per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed. | Up to 3 years post registration |