A Clinical Trial of the P-Glycoprotein Antagonist, XR9576, in Combination With Vinorelbine in Patients With Cancer: Analysis of the Interaction Between XR9576 and Vinorelbine
N/A
N/A
Both
Breast Cancer, Cancer, Lung Cancer, Ovarian Cancer
Trial Information
A Clinical Trial of the P-Glycoprotein Antagonist, XR9576, in Combination With Vinorelbine in Patients With Cancer: Analysis of the Interaction Between XR9576 and Vinorelbine
Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer.
Accumulating evidence indicates that in some malignancies P-glycoprotein can confer
resistance, and that its reversal can improve therapeutic outcome. Clinical trials
investigating P-glycoprotein antagonists have been hampered by the occurrence of
unpredictable pharmacokinetic interactions, which have required dose reductions of the
chemotherapeutic agents to avert excessive toxicity. XR9576 is a new P-glycoprotein
antagonist that is more potent, has prolonged activity, and is potentially devoid of
significant pharmacokinetic interactions. This phase I study seeks to identify the safety
of XR9576 administration in combination with vinorelbine and determine the extent, if any,
of a pharmacokinetic interaction between these two drugs. Clinical responses will also be
determined.
Inclusion Criteria
Age greater than or equal to 18 years.
Histologic or cytologic confirmation of cancer, for which there is no known standard
therapy capable of extending life expectancy.
Performance status ECOG 0-2.
Life expectancy of 3 months or greater.
Platelet count greater than or equal to 90,000/mL.
Absolute granulocyte count (AGC) greater than or equal to 1,000/mL.
Serum creatinine less than or equal to 1.5 mg/dl (or if greater than 1.5, measured
creatinine clearance greater than or equal to 50 mL/min).
SGPT and SGOT less than or equal to 2.5 times normal limit, and bilirubin less than or
equal to 1.5 times normal limit (in patients with clinical evidence of Gilbert's disease,
less than or equal to 3 times normal limit).
2 weeks from prior radiation or chemotherapy and recovery from associated toxicities such
that they meet eligibility criteria. Hormonal therapy may be taken up to the time of
enrollment.
No serious intercurrent medical illness.
Bidimensionally measurable disease by radiographic means or physical examination; or
relevant tumor markers (i.e. CA-125 and PSA greater than or equal to 2 times upper limit
of normal).
The ability to understand and willingness to sign a written informed consent form, and to
comply with the protocol.
No pregnant or nursing women; or women of childbearing potential unless using effective
contraception as determined by the patient's physician.
No history of another malignancy; specifically, no patients with a non-skin malignancy or
with melanoma within the past 5 years; no concomitant malignancy that has not been
curatively treated. However, cancer survivors who have undergone potentially curative
therapy for a prior malignancy at least 5 years before enrollment is considered, and are
deemed at low risk for recurrence by their treating physicians.
No patients with current or a history of CNS metastases.
No patients who are a poor medical risk because of other non malignant systemic disease or
active, uncontrolled infection.
No HIV seropositive patients.
No prior vinorelbine therapy.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Authority:
United States: Federal Government
Study ID:
000044
NCT ID:
NCT00001944
Start Date:
December 1999
Completion Date:
June 2001
Related Keywords:
- Breast Cancer
- Cancer
- Lung Cancer
- Ovarian Cancer
- Drug Resistance
- MDR-1
- P-Glycoprotein Blocker
- Pgp
- Resistance Reversal
- Breast Neoplasms
- Lung Neoplasms
- Ovarian Neoplasms
Name | Location |
|---|---|
| National Cancer Institute (NCI) | Bethesda, Maryland 20892 |
