Clinical trial NCT00216099
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Sponsor: Christopher Sweeney, MBBS
Start date: 2005-02-01; Completion date: 2009-03-01
Enrollment: 49 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Docetaxel-based therapy has been shown to prolong survival as first-line therapy for patients with hormone refractory prostate cancer (HRPC), and has become the standard of care. The beneficial effects of any therapy in HRPC may be diverse and include reduction in tumor bulk (when measurable), reduction in prostate-specific antigen PSA, reduction in symptoms (particularly pain), or stabilization of disease. Clear reductions in tumor bulk or PSA may provide objective evidence of a treatment effect, and stabilization of disease may be just as clinically meaningful in patients who are actively progressing prior to starting therapy. Pemetrexed has shown a broad array of activity in many diseases that until now were thought to be non-responsive to chemotherapy in the second-line setting.

This trial is designed to further assess the efficacy, safety, tolerability, and pharmacogenetics of pemetrexed as a single agent in subjects with HRPC whose disease has progressed following one prior taxane-based chemotherapy regimen for HRPC.

Detailed description:
OUTLINE: This is a multi-center study.

* Pemetrexed 500mg/m2 will be administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle.
* Folic Acid (350-1000 mcg. PO daily) will be taken by patients to reduce toxicity. At least 5 daily doses of folic acid must be taken during the 7-day period preceding the first dose of pemetrexed, and dosing should continue during the full course of therapy and for 21 days after the last dose of pemetrexed.
* Vitamin B12 (1000 µg) will be administered as an intramuscular injection during the week preceding the first dose of pemetrexed and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed.

Performance Status: Karnofsky Performance Status 70-100

Life expectancy \> 12 weeks

Hematopoietic:

* Absolute Neutrophil Count (ANC) \> 1500/mm3
* Platelet count \> 100,000/mm3
* Hemoglobin \> 9 g/dL

Hepatic:

* Bilirubin \< 1.5 X upper limit of normal (unless due to Gilbert's disease)
* Alkaline phosphatase and Alanine Transanimase (ALT) (SGPT) \< 3 X upper limit of normal (ULN); may be \< 5 X ULN for patients with liver metastases. Alkaline phosphatase may be any value for patients with bone metastases.

Renal:

* Calculated creatinine clearance \>45 mL/min based on the standard Cockroft and Gault formula

Cardiovascular:

* No congestive heart failure requiring therapy or New York Heart Association (NYHA) class II or greater or active angina or known myocardial infarction within 12 months prior to study
* No unstable angina, uncontrolled congestive heart failure, or unstable symptomatic arrhythmia requiring medication within 6 months prior to being registered for protocol therapy
* Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible

Pulmonary:

* Not specified

Arms: arm 1: * Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
* Oral Folic Acid, once per day for 7 days preceding pemetrexed dose, continued daily, and for 21 days after the last dose of pemetrexed.
* Vitamin B12, 1000ug intramuscular injection 7 days preceding pemetrexed dose, and every three cycles thereafter on the same day of pemetrexed administration
Interventions: intervention 1: Pemetrexed intervention 2: Folic Acid intervention 3: Vitamin B12
Intervention descriptions: intervention 1: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle intervention 2: All participants received oral Folic Acid 350-100ug once per day for 7 days preceding the first pemetrexed dose and continuing throughout the study and and for 21 days after the last dose of pemetrexed. intervention 3: All patients received vitamin B12 1000ug intramuscular injection the week preceding the first pemetrexed dose and received additional 1000ug intramuscular injections every three cycles thereafter on the same day of pemetrexed administration.

Protocol documents: