Lung-MAP: Taselisib as Therapy in Treating Patients With Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well taselisib (GDC-0032) works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the phosphoinositide 3-kinase (PI3K) biomarker. PI3K can cause tumor cells to grow more quickly. Taselisib may decrease the activity of PI3K and may be able to shrink tumors.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Phase II Component: To evaluate if there is sufficient evidence to continue to the phase III component by evaluating the objective response rate (ORR) for PI3K Genentech (GNE)-positive patients registered to S1400B treated with GDC-0032. (Phase II) II. Phase III Component: If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized phase III trial. SECONDARY OBJECTIVES: I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in both the subset of patients defined to be PI3K GNE-positive and in the entire S1400B (PI3K Foundation Medicine [FMI] positive) study population treated with GDC-0032. (Phase II) II. To evaluate ORR in the entire S1400B (PI3K FMI positive) study population treated with GDC-0032 to evaluate the duration of response (DoR) both in GNE positive and FMI positive. (Phase II) III. To evaluate the DoR both in the entire S1400B PI3K FMI positive study population and in GNE positive patients treated with GDC-0032 who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. (Phase II) IV. To evaluate the frequency and severity of toxicities associated with GDC-0032. (Phase II) TRANSLATIONAL MEDICINE OBJECTIVES: I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the GDC-0032 beyond the chosen biomarker for biomarker-driven sub-studies. II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/ blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung. OUTLINE: As of 12/18/2015, patients are assigned to Arm I. 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 intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III. Re-registration ARM III: Patients in Arm II eligible for re-registration receive taselisib orally (PO) on days 1-21. Courses repeat every 21 days 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
-----------------
A Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)

Conditions
-----------------
Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma

Intervention / Treatment
-----------------
* Other: Laboratory Biomarker Analysis
* Drug: Taselisib


Participation Criteria
=================
Eligibility Criteria
-----------------
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 be assigned to S1400B Hemoglobin A1c (HbA1c) < 7% obtained within 28 days prior to sub-study registration Fasting glucose < 125 mg/dL obtained within 28 days prior to sub-study registration Patients must not have type I or II diabetes that requires anti-hyperglycemic medication 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 also be offered participation in banking for future use of specimens STEP 2 TO GDC-0032 RE-REGISTRATION: Patients must have progressed on arm 2 (docetaxel) of this sub-study Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to step 2 re-registration; patients must have recovered (< grade 1) from any side effects of prior therapy Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined 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 step 2 re-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 step 2 re-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 step 2 re-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 (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 1 day prior to re-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 step 2 re-registration Platelet count >= 100,000 mcl obtained within 28 days prior to step 2 re-registration Hemoglobin >= 9 g/dL obtained within 28 days prior to step 2 re-registration Serum bilirubin =< institutional upper limit of normal (IULN); for patients with liver metastases, bilirubin must be =< 5 x IULN obtained within 28 days prior to step 2 re-registration Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to step 2 re-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) HbA1c < 7% obtained within 28 days prior to step 2 re-registration Fasting glucose < 125 mg/dL obtained within 28 days prior to step 2 re-registration Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min Patients must have Zubrod performance status of 0-1 documented within 28 days prior to step 2 re-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 pneumonia [PCP] prophylaxis); must not be newly diagnosed within 12 months prior to re-registration Prestudy history and physical exam must be obtained within 28 days prior to re-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 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (GDC-0032)<br>Patients receive taselisib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Taselisib<br>* Given PO<br>* Other names: GDC-0032;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) for PI3K GNE-positive Participants Registered to S1400B Treated With GDC-0032. | ORR-the percentage of PI3K GNE-positive participants with confirmed and unconfirmed, partial response and complete response to treatment with GDC-0032 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). | From date of registration to maximum of 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed Progression Free Survival (IA-PFS) in Both the Subset of Participants Defined to be PI3K GNE-positive and in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032. | 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. | From time of registration to maximum of 3 years. | 
| Investigator-assessed Overall Survival (OS) in Both the Subset of Participants Defined to be PI3K GNE-positive and in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032. | From date of sub-study registration to date of death due to any cause assessed by local review. | From time of registration to maximum of 3 years. | 
| ORR in the Entire S1400B (PI3K FMI Positive) Study Population Treated With GDC-0032. | Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). | From time of registration to maximum of 3 years. | 
| Duration of Response (DoR) Both in the Entire S1400B PI3K FMI Positive Study Population and in GNE Positive Participants Treated With GDC-0032 Who Achieve a CR or PR (Confirmed and Unconfirmed) by RECIST 1.1. | Among participants who had a response, duration is calculated from registration to response date. | From time of registration to maximum of 3 years. | 
| Frequency and Severity of Toxicities Associated With GDC-0032. (Phase II) | Frequency and severity of toxicities greater than Grade 2 associated with GDC-0032. | From date of registration to maximum of 3 years. |