PD-0332991, 5-FU, and Oxaliplatin for Advanced Solid Tumor Malignancies

NCT01522989 | Unknown Phase 1 DMC

• 2 other identifiers: 2011-219WS1877559
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for patients with advanced solid tumor malignancies (cancer that has spread to other parts of the body). The purpose of this study is to test the safety and effectiveness of a new combination of drugs, PD-0332991 and 5-Fluorouracil and Oxaliplatin for patients with advanced solid tumor malignancies . PD-0332991 stops cells from dividing by blocking an enzyme called cyclin-dependent kinase (CDK), which cancer cells need to grow and divide. By inhibiting this enzyme, PD-0332991 prevent cancer cells from growing and dividing, while the 5-Fluorouracil and Oxaliplatin damage the cells, hopefully increasing the killing of cancer cells, thus decreasing the tumors in the body. PD-0332991 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration for use in colorectal cancer. It is given as a pill which is taken once a day for one week followed by one week off. 5-Fluorouracil and Oxaliplatin are administered as an infusion into a vein once every 2 weeks and are approved for and used as chemotherapy for several cancers.

Conditions

Advanced Solid Tumor Malignancies

Keywords

Cancer; Advanced; Refractory

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 dose and schedule

  The dose and schedule of PD-0332991 to be used in combination with 5-FU

  18 months

Secondary Outcomes (5)

• Toxicity of the combination of PD-0332991, 5-FU, and oxaliplatin

  18 months

• Pharmacodynamics

  18 months

• Response rate

  18 months

• Disease control rate

  4 months

• Trough level of PD-0332991 on Day 1 of Cycles 1-4

  4 months

Study Arms (1)

PD-0332991, 5-FU and oxaliplatin

EXPERIMENTAL

PD-0332991 with 5-FU and oxaliplatin

Drug: PD-0332991; Drug: 5-FU; Drug: Oxaliplatin

Interventions

PD-0332991 DRUG

Stage 1: PD-0332991 daily Days 1-7 in escalating doses 5-FU 400 mg/m2 Day 8 Leucovorin 400 mg/M2 Day 8 5-FU continuous Infusion over 46 hours, 2400 mg/M2 Days 8-10 Stage 2: 3 cohorts of subjects each will be treated with the dose of PD-0332991 determined to be the recommended Phase 2 dose in Stage 1 of the study with 5-FU at the doses above but on different schedules: Cohort 1: 5-FU bolus on Day 7 and infusion Days 7-9 Cohort 2: 5-FU bolus Day 9 and infusion Days 9-11 Cohort 3: 5-FU bolus Day 1 and infusion Days 1-3 In Stage 3, PD-0332991 and 5-FU will be given at the doses and schedule determined in Stages 1 and 2 of this study with the addition of oxaliplatin 85 mg/m2 given on the same day as the 5-FU bolus.

Also known as: Palbociclib

PD-0332991, 5-FU and oxaliplatin

5-FU DRUG

Stage 1: PD-0332991 daily Days 1-7 in escalating doses 5-FU 400 mg/m2 Day 8 Leucovorin 400 mg/M2 Day 8 5-FU continuous Infusion over 46 hours, 2400 mg/M2 Days 8-10 Stage 2: 3 cohorts of subjects each will be treated with the dose of PD-0332991 determined to be the recommended Phase 2 dose in Stage 1 of the study with 5-FU at the doses above but on different schedules: Cohort 1: 5-FU bolus on Day 7 and infusion Days 7-9 Cohort 2: 5-FU bolus Day 9 and infusion Days 9-11 Cohort 3: 5-FU bolus Day 1 and infusion Days 1-3 In Stage 3, PD-0332991 and 5-FU will be given at the doses and schedule determined in Stages 1 and 2 of this study with the addition of oxaliplatin 85 mg/m2 given on the same day as the 5-FU bolus.

Also known as: 5-Fluorouracil

PD-0332991, 5-FU and oxaliplatin

Oxaliplatin DRUG

Stage 1: PD-0332991 daily Days 1-7 in escalating doses 5-FU 400 mg/m2 Day 8 Leucovorin 400 mg/M2 Day 8 5-FU continuous Infusion over 46 hours, 2400 mg/M2 Days 8-10 Stage 2: 3 cohorts of subjects each will be treated with the dose of PD-0332991 determined to be the recommended Phase 2 dose in Stage 1 of the study with 5-FU at the doses above but on different schedules: Cohort 1: 5-FU bolus on Day 7 and infusion Days 7-9 Cohort 2: 5-FU bolus Day 9 and infusion Days 9-11 Cohort 3: 5-FU bolus Day 1 and infusion Days 1-3 In Stage 3, PD-0332991 and 5-FU will be given at the doses and schedule determined in Stages 1 and 2 of this study with the addition of oxaliplatin 85 mg/m2 given on the same day as the 5-FU bolus.

Also known as: Eloxatin

PD-0332991, 5-FU and oxaliplatin

Eligibility Criteria

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

You may qualify if:

• Retinoblastoma-positive, histologically proven advanced solid tumor malignancies for which no curative therapy exists
• Biopsy accessible tumor deposits
• Corrected QT interval less than 500 milliseconds by EKG
• ECOG preformance status 0-2
• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease and have not had treatment with steroids within 1 week of study enrollment.
• Adequate hepatic, bone marrow, and renal function
• Partial thromboplastin time must be \</= 1.5 x upper limit normal range and INR \< 1.5. Subjects on anticoagulant will be permitted to enroll as long as the INR is in acceptable therapeutic range.
• Life expectancy \> 12 weeks
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months.
• Subject is capable of understanding and complying with parameters of the protocol and able to sign and date the informed consent.

You may not qualify if:

• Intolerant of, or ineligible for 5-FU, oxaliplatin and/or the combination of both
• Peripheral neuropathy \>/= Grade 2 at baseline or peripheral neuropathy \>/= Grade 1 with neuropathic pain
• Active severe infection or known chronic infection with HIV or hepatitis B virus
• Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia or myocardial infarction, stroke, or congestive heart failure within the last 6 months.
• Life-threatening visceral disease or other severe concurrent disease
• Women who are pregnant or breastfeeding
• Anticipated patient survival under 3 months
• Concurrent use of known CYP 3A4 inhibiting or activating medications
• Clinically significant and uncontrolled major medical condition(s)

Sponsors & Collaborators

• Georgetown University: lead
• Pfizer: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

palbociclib; Fluorouracil; Oxaliplatin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Michael Pishvaian, MD PhD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: February 1, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 4, 2020

Record last verified: 2019-05

Locations

US (1)