This phase II/III trial studies how well palbociclib works in treating cell cycle gene alteration positive 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 cell cycle gene alterations which can cause tumor cells to grow more quickly. Palbociclib may slow cell cycle progression 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) for cell cycle gene alteration positive patients registered to S1400C treated with palbociclib. (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) of cell cycle gene alteration-positive patients treated with palbociclib. (Phase II) II. To evaluate the duration of response (DoR) among cell cycle gene alteration positive patients treated with palbociclib 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 palbociclib. (Phase II) TRANSLATIONAL MEDICINE OBJECTIVES: I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to palbociclib 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 09/01/2016, all arms are closed to accrual. ARM I (CLOSED TO ACCRUAL 09/01/2016): Patients receive palbociclib orally (PO) on days 1-21. Courses repeat every 28 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 (CLOSED TO ACCRUAL 09/01/2016): Patients in Arm II eligible for re-registration receive palbociclib PO on days 1-21. Courses repeat every 28 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
53
Given IV (arm II closed to accrual 12/18/2015)
Correlative studies
Given PO
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
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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 palbociclib 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 palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: From date of registration to progression or treatment discontinuation, up to 2 years and 10 months.
Duration of Response Among Participants 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 participants who achieve a complete or partial response. 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 palbociclib 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 10 months or death
Overall Survival With Investigational Therapy
From date of sub-study registration until death due to any cause. It was pre-specified that only the palbociclib 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 10 months or death
Progression-free Survival With Palbociclib.
From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. It was pre-specified that only the palbociclib 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 10 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 palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment
Time frame: Duration of treatment and follow up to a maximum of 2 years and 10 months post registration or death
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