Clinical trial NCT01522989: PD-0332991, 5-FU, and Oxaliplatin for Advanced Solid Tumor Malignancies
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor Malignancies
Keywords: Cancer
Advanced
Refractory
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2012-02-01
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Recommended Phase 2 dose and schedule
timeFrame: 18 months
Secondary outcomes:
measure: Toxicity of the combination of PD-0332991, 5-FU, and oxaliplatin
timeFrame: 18 months
measure: Pharmacodynamics
timeFrame: 18 months
measure: Response rate
timeFrame: 18 months
measure: Disease control rate
timeFrame: 4 months
measure: Trough level of PD-0332991 on Day 1 of Cycles 1-4
timeFrame: 4 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: Michael Pishvaian, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: