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

Sponsor

Georgetown University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01522989

Collaborator

Pfizer (Industry)

Enrollment

Location

Arm

108

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Malignancies	Drug: PD-0332991 Drug: 5-FU Drug: Oxaliplatin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of the CDK4/6 Inhibitor PD-0332991, 5-Fluorouracil, and Oxaliplatin in Patients With Advanced Solid Tumor Malignancies

Study Start Date :

Dec 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-0332991, 5-FU and oxaliplatin PD-0332991 with 5-FU and oxaliplatin	Drug: PD-0332991 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. Other Names: Palbociclib Drug: 5-FU 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. Other Names: 5-Fluorouracil Drug: Oxaliplatin 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. Other Names: Eloxatin

Arm

Intervention/Treatment

Experimental: PD-0332991, 5-FU and oxaliplatin

PD-0332991 with 5-FU and oxaliplatin

Drug: PD-0332991

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.

Other Names:

Palbociclib

Drug: 5-FU

Other Names:

5-Fluorouracil

Drug: Oxaliplatin

Other Names:

Eloxatin

Outcome Measures

Primary Outcome Measures

Recommended Phase 2 dose and schedule [18 months]
The dose and schedule of PD-0332991 to be used in combination with 5-FU

Secondary Outcome Measures

Toxicity of the combination of PD-0332991, 5-FU, and oxaliplatin [18 months]
To quantify the adverse events
Pharmacodynamics [18 months]
evaluation of the effects of schedule of therapy on pharmacodynamic measures of PD-0332991 activity
Response rate [18 months]
Response rate as determined by RECIST 1.1
Disease control rate [4 months]
Stable disease after four cycles + partial response + complete response
Trough level of PD-0332991 on Day 1 of Cycles 1-4 [4 months]
Determination of the effects of 5-FU on pharmacokinetics of PD-0332991

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

Intolerant of, or ineligible for 5-FU, oxaliplatin and/or the combination of both
CNS metastases that do not meet the criteria outlined in the inclusion criteria
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)