This phase I trial studies the side effects and best dose of palbociclib with cisplatin or carboplatin in treating patients with solid tumors that have spread to other places and usually cannot be cured or controlled with treatment. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib with cisplatin or carboplatin may help stop tumor growth in patients with advanced solid tumors.
PRIMARY OBJECTIVES: I. Assess the safety and tolerability of palbociclib when administered along with cisplatin or carboplatin. II. Establish the recommended phase 2 dose (RP2D) of the tested combinations. SECONDARY OBJECTIVES: I. Characterize the pharmacokinetic (PK) profiles of cisplatin, carboplatin. II. Obtain preliminary evidence of anti-tumor efficacy of the tested combination regimens. III. Conduct PK/pharmacodynamics (PD) correlative analyses using palbociclib trough concentration and cyclin-dependent kinase 4 (CDK4) inhibition read-outs in tumor and surrogate samples collected on course 1 day 22 (C1D22). IV. Assess potential association between tissue-based biomarkers and efficacy. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms. ARM A: Patients receive cisplatin intravenously (IV) over 30-60 minutes on day 1 and palbociclib orally (PO) once daily (QD) on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive carboplatin IV over 30-60 minutes on day 1 and palbociclib PO QD on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for up to 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Study completion, an average of 2 years
Incidence of dose limiting toxicities defined as grade 3 or higher toxicity
Time frame: Up to 4 weeks
Recommended phase 2 dose (RP2D) as the highest doses of palbociclib and cisplatin or palbociclib and carboplatin
Time frame: Study completion, an average of 2 years
Overall response rate (complete response + partial response) assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria
Will be summarized and presented along with 95% exact confidence intervals.
Time frame: Up to 3 years
Pharmacokinetic (PK) characteristics of carboplatin including maximum concentration (Cmax)
Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.
Time frame: Up to 4 weeks
Pharmacokinetic (PK) characteristics of cisplatin including maximum concentration (Cmax)
Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.
Time frame: Up to 4 weeks
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