Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

NCT02897375 | Completed Phase 1 DMC

• 4 other identifiers: IRB00089583NCI-2016-01037Winship3263-16P30CA138292
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Overall response rate (complete response + partial response) assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria

  Up to 3 years

• Pharmacokinetic (PK) characteristics of carboplatin including maximum concentration (Cmax)

  Up to 4 weeks

• Pharmacokinetic (PK) characteristics of cisplatin including maximum concentration (Cmax)

  Up to 4 weeks

Study Arms (2)

Arm A (palbociclib, cisplatin)

EXPERIMENTAL

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; Drug: Palbociclib

Arm B (palbociclib, carboplatin)

EXPERIMENTAL

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; Drug: Palbociclib

Interventions

Carboplatin DRUG

Given IV

Also known as: Paraplatin

Arm B (palbociclib, carboplatin)

Cisplatin DRUG

Given IV

Also known as: CDDP, Cis-diamminedichloridoplatinum, Cisplatinum, Cismaplat, Neoplatin

Arm A (palbociclib, cisplatin)

Palbociclib DRUG

Given PO

Also known as: Ibrance, PD-0332991

Arm A (palbociclib, cisplatin); Arm B (palbociclib, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Pfizer: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Alese OB, Harvey RD, Wu C, Hitron E, Collins H, Scott S, Steuer C, Bilen MA, Carthon BC, Switchenko JM, Ramalingam SS, Owonikoko TK. Phase I study of palbociclib with cisplatin or carboplatin in the management of patients with advanced pancreatic cancer. Oncologist. 2025 Oct 1;30(10):oyaf284. doi: 10.1093/oncolo/oyaf284.

  PMID: 40973049 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Sarcoma; Colorectal Neoplasms; Head and Neck Neoplasms; Urinary Bladder Neoplasms; Ovarian Neoplasms

Interventions

Carboplatin; Cisplatin; palbociclib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Olatunji B Alese, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 13, 2016
• Study Start: October 24, 2016
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (1)