Palbociclib With Cisplatin Or Carboplatin In Advanced Solid Tumors

Study Overview

Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

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.

Solid Neoplasm
Stage III Pancreatic Cancer
Stage IIIA Breast Cancer
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIB Breast Cancer
Stage IIIB Non-Small Cell Lung Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IVA Pancreatic Cancer
Stage IVB Pancreatic Cancer
Sarcoma
Colorectal Cancer
Head and Neck Cancer
Cancer of Unknown Primary
Bladder Cancer
Ovarian Cancer

DRUG: Carboplatin
DRUG: Cisplatin
DRUG: Palbociclib

IRB00089583
NCI-2016-01037 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
Winship3263-16 (OTHER Identifier) (OTHER: Emory University/Winship Cancer Institute)
P30CA138292 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-08-30	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-10-06
First Submitted that Met QC Criteria 2016-09-07	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-10-10
First Posted (ACTUAL) 2016-09-13	Results First Posted N/A	Last Verified 2023-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A (palbociclib, cisplatin) Patients receive cisplatin 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.	DRUG: Cisplatin Given IV DRUG: Palbociclib Given PO
EXPERIMENTAL: Arm B (palbociclib, carboplatin) 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.	DRUG: Carboplatin Given IV DRUG: Palbociclib Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm A (palbociclib, cisplatin)

Patients receive cisplatin 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.

DRUG: Cisplatin

Given IV

DRUG: Palbociclib

Given PO

EXPERIMENTAL: Arm B (palbociclib, carboplatin)

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.

DRUG: Carboplatin

Given IV

DRUG: Palbociclib

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0		Study completion, an average of 2 years
Incidence of dose limiting toxicities defined as grade 3 or higher toxicity		Up to 4 weeks
Recommended phase 2 dose (RP2D) as the highest doses of palbociclib and cisplatin or palbociclib and carboplatin		Study completion, an average of 2 years

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	Up to 4 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have histologically or cytologically confirmed solid organ malignancy
Patients enrolled in the expansion cohort must have histologically or cytologically confirmed squamous non-small cell lung cancer (NSCLC), breast or pancreaticobiliary tract cancer
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) with conventional techniques or as ≥ 10 mm (≥ 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
Leukocytes ≥ 3,000/mL
Absolute neutrophil count ≥ 1,500/mL
Platelets ≥ 100,000/mL
Hemoglobin ≥ 10 g/dL
Total bilirubin ≤ 1.5 × institutional upper limit of normal (except for patients with Gilbert disease)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (up to 5 X upper limit of normal [ULN] for patients with liver metastasis)
Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of study drug administration
Ability to understand and the willingness to sign a written informed consent document

Patients who have had cytotoxic anticancer chemotherapy or immune checkpoint inhibitor within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or palliative radiation within 2 weeks (stereotactic radiation therapy [SRS] for brain metastasis within 48 hours) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Patients receiving cytotoxic agent as immunomodulatory therapy for a non neoplastic indication (e.g. methotrexate for rheumatoid arthritis) and who are unable to discontinue such agents within 2 weeks prior to starting treatment
Oral targeted therapy within five days or five half-lives, whichever is longer, prior to initiating protocol therapy treatment
Patients who are receiving any other investigational agents
Use of strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors and inducers
Patients with symptomatic uncontrolled brain metastases are excluded; (patients with stable treated or asymptomatic untreated brain metastasis not requiring glucocorticoids are allowed)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib, carboplatin or cisplatin
Concurrent administration of strong inducers and inhibitors of CYP3A enzyme or CYP3A substrates with narrow therapeutic window
Uncontrolled intercurrent illness including, but not limited to:

Ongoing or active infection requiring intravenous antibiotics at the time of treatment initiation
Symptomatic congestive heart failure (requiring hospital stay within the last 6 months)
Myocardial infarction within the last 6 months
Unstable angina pectoris, cardiac arrhythmia
Psychiatric illness
Social situations or circumstances that would limit compliance with study requirements
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with palbociclib
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Pfizer
National Institutes of Health (NIH)
National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Olatunji B Alese, MD, Emory University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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