Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

Sponsor

Emory University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02897375

Collaborator

Pfizer (Industry)

Enrollment

Location

Arms

85.2

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

Assess the safety and tolerability of palbociclib when administered along with cisplatin or carboplatin.
Establish the recommended phase 2 dose (RP2D) of the tested combinations.

SECONDARY OBJECTIVES:

Characterize the pharmacokinetic (PK) profiles of cisplatin, carboplatin.
Obtain preliminary evidence of anti-tumor efficacy of the tested combination regimens.
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).
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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Palbociclib in Combination With Cisplatin or Carboplatin in Advanced Solid Malignancies

Actual Study Start Date :

Oct 24, 2016

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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 Other Names: CDDP Cis-diamminedichloridoplatinum Cisplatinum Cismaplat Neoplatin Drug: Palbociclib Given PO Other Names: Ibrance PD-0332991
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 Other Names: Paraplatin Drug: Palbociclib Given PO Other Names: Ibrance PD-0332991

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

Other Names:

CDDP

Cis-diamminedichloridoplatinum

Cisplatinum

Cismaplat

Neoplatin

Drug: Palbociclib

Given PO

Other Names:

Ibrance

PD-0332991

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

Other Names:

Paraplatin

Drug: Palbociclib

Given PO

Other Names:

Ibrance

PD-0332991

Outcome Measures

Primary Outcome Measures

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

Overall response rate (complete response + partial response) assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria [Up to 3 years]
Will be summarized and presented along with 95% exact confidence intervals.
Pharmacokinetic (PK) characteristics of carboplatin including maximum concentration (Cmax) [Up to 4 weeks]
Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.
Pharmacokinetic (PK) characteristics of cisplatin including maximum concentration (Cmax) [Up to 4 weeks]
Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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