This phase II/III trial studies how well FGFR inhibitor AZD4547 (AZD4547) 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 fibroblast growth factor receptor (FGFR) biomarker. FGFR can cause tumor cells to grow more quickly. AZD4547 may decrease the activity of FGFR and may be able to shrink tumors.

NCT02965378

Conditions

1. FGFR1 Gene Amplification
2. FGFR1 Gene Mutation
3. FGFR2 Gene Amplification
4. FGFR2 Gene Mutation
5. FGFR3 Gene Amplification
6. FGFR3 Gene Mutation
7. Recurrent Squamous Cell Lung Carcinoma
8. Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

1. Drug: Docetaxel
2. Drug: FGFR Inhibitor AZD4547
3. Other: Laboratory Biomarker Analysis

MeSH:Carcinoma Lung Neoplasms

HPO:Carcinoma Neoplasm of the lung

Will be monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to receive.. 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 S1400D - 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 or foods that are known to be strong/moderate CYP3A4 or CYP2D6 inhibitors and/or inducers - Patients must not have received nitrosourea or mitomycin C within 42 days prior to sub-study registration - 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); performed within 28 days prior to sub-study registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. --- S1400D ---

complete left bundle branch block, third degree heart block); patients must not have 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 - 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 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) - Patients must have a serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the Cockroft-Gault formula - 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: 1. Must have undetectable viral load using standard HIV assays in clinical practice; 2. Must have cluster of differentiation (CD)4 count >= 400/mcL; 3. Must not require prophylaxis for any opportunistic infections (i.e., fungal, mycobacterium avium complex [mAC], or pneumocystis pneumonia [PCP] prophylaxis); 4. 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 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 S1400D - 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 or foods that are known to be strong/moderate CYP3A4 or CYP2D6 inhibitors and/or inducers - Patients must not have received nitrosourea or mitomycin C within 42 days prior to sub-study registration - 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); performed within 28 days prior to sub-study registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. --- S1400D ---

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.

NCT02154490

Conditions

1. Recurrent Squamous Cell Lung Carcinoma
2. Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

1. Drug: Docetaxel
2. Biological: Durvalumab
3. Drug: Erlotinib Hydrochloride
4. Drug: FGFR Inhibitor AZD4547
5. Biological: Ipilimumab
6. Other: Laboratory Biomarker Analysis
7. Biological: Nivolumab
8. Drug: Palbociclib
9. Other: Pharmacological Study
10. Biological: Rilotumumab
11. Drug: Talazoparib
12. Drug: Taselisib
13. Biological: Tremelimumab

MeSH:Carcinoma Lung Neoplasms

HPO:Carcinoma Neoplasm of the lung

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). --- S1400D ---