PD-0332991, 5-FU, and Oxaliplatin for Advanced Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Georgetown University
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
First received: December 20, 2011
Last updated: February 12, 2014
Last verified: February 2014

This study is for patients with metastatic colorectal cancer (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 metastatic colorectal cancer. 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 colorectal cancer.

Condition Intervention Phase
Colorectal Cancer
Drug: PD-0332991, 5-FU, oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Refractory Colorectal Cancer

Resource links provided by NLM:

Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Recommended Phase 2 dose and schedule [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The dose and schedule of PD-0332991 to be used in combination with 5-FU

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To quantify the adverse events

  • Pharmacodynamics [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    evaluation of the effects of schedule of therapy on pharmacodynamic measures of PD-0332991 activity

  • Response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Response rate as determined by RECIST 1.1

  • Disease control rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Stable disease after four cycles + partial response + complete response

  • Trough level of PD-0332991 on Day 1 of Cycles 1-4 [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Determination of the effects of 5-FU on pharmacokinetics of PD-0332991

Estimated Enrollment: 37
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PD-0332991, 5-FU and oxaliplatin
PD-0332991 with 5-FU and oxaliplatin
Drug: PD-0332991, 5-FU, 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
  • 5-Fluorouracil


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Retinoblastoma-positive, histologically proven colorectal cancer with measurable disease
  • Progression on, or intolerance of, or ineligibility for all standard therapies (including regimens containing fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an anti-EGFR antibody (where appropriate).
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522989

Contact: Ion Cotarla 202-687-4510 ic34@georgetown.edu
Contact: Christine Fasano, RN 202-687-2007 ccf42@georgetown.edu

United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Ion Cotarla    202-687-4510    ic34@georgetown.edu   
Contact: Christine Fasano, RN    202-687-2007    cff42@georgetown.edu   
Principal Investigator: Michael Pishvaian, MD PhD         
Sponsors and Collaborators
Georgetown University
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01522989     History of Changes
Other Study ID Numbers: 2011-219, WS1877559
Study First Received: December 20, 2011
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014