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.
PRIMARY OBJECTIVES: I. To evaluate if there is sufficient evidence to continue to the Phase III component by evaluating the objective response rate (ORR) with AZD4547 in FGFR-positive patients. (Phase II) II. If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized Phase III trial. (Phase III) SECONDARY OBJECTIVES: I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in FGFR-positive patients treated with AZD4547. (Phase II) II. To evaluate the duration of response (DoR) among FGFR positive patients treated with AZD4547 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) III. To evaluate the frequency and severity of toxicities associated with AZD4547 in FGFR positive patients. (Phase II) TRANSLATIONAL MEDICINE OBJECTIVES: I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the AZD4547 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 FGFR inhibitor AZD4547 orally (PO) twice daily (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 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. ARM III: Patients in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
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Alaska Oncology and Hematology LLC
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Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)
The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with AZD4547 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. It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: From date of registration to maximum of 2 years and 4 months or death.
Duration of Response Among Patients Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1
From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review, or symptomatic deterioration or death due to any cause among patients who achieve complete or partial response per RECIST v1.1. 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. 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 a measurable increase in a non-target lesion, or the appearance of new lesions. It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: From date of registration to maximum of 2 years and 4 months or death.
Overall Survival
From date of sub-study registration on study until death from any cause. Observations for participants last known to be alive were censored. It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: From date of registration to maximum of 2 years and 4 months or death
Progression-free Survival
From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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 a measurable increase in a non-target lesion, or the appearance of new lesions. It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: From date of registration to maximum of 2 years and 4 months or death.
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported per CTCAE Version 5.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: Duration of treatment and follow up, up to 2 years and 4 months post registration or death.
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