- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02897375
Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors
A Phase 1 Study of Palbociclib in Combination With Cisplatin or Carboplatin in Advanced Solid Malignancies
Study Overview
Status
Conditions
- Sarcoma
- Head and Neck Cancer
- Stage IIIA Non-Small Cell Lung Cancer
- Stage IIIB Non-Small Cell Lung Cancer
- Colorectal Cancer
- Ovarian Cancer
- Bladder Cancer
- Stage IV Non-Small Cell Lung Cancer
- Stage III Pancreatic Cancer
- Stage IV Breast Cancer
- Stage IIIA Breast Cancer
- Stage IIIB Breast Cancer
- Stage IIIC Breast Cancer
- Stage IVA Pancreatic Cancer
- Stage IVB Pancreatic Cancer
- Solid Neoplasm
- Cancer of Unknown Primary
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Emory University/Winship Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
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.
|
Given IV
Other Names:
Given PO
Other Names:
|
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.
|
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
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
|
Study completion, an average of 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (complete response + partial response) assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria
Time Frame: Up to 3 years
|
Will be summarized and presented along with 95% exact confidence intervals.
|
Up to 3 years
|
Pharmacokinetic (PK) characteristics of carboplatin including maximum concentration (Cmax)
Time Frame: Up to 4 weeks
|
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)
Time Frame: Up to 4 weeks
|
Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.
|
Up to 4 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olatunji B Alese, MD, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Skin Diseases
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Breast Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Pancreatic Diseases
- Breast Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Carboplatin
- Palbociclib
Other Study ID Numbers
- IRB00089583
- P30CA138292 (U.S. NIH Grant/Contract)
- NCI-2016-01037 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- Winship3263-16 (Other Identifier: Emory University/Winship Cancer Institute)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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