Official Title: “A Phase II Study of Pemetrexed (Alimta) as Second-Line Therapy for Hormone Refractory Prostate Cancer: Hoosier Oncology Group GU03-67”

Docetaxel-based therapy has been shown to prolong survival as first-line therapy for patients with 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 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.

Study Type: Interventional

Study Design: Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2009

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: - 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 ALT (SGPT) < 3 X upper limit of normal; 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 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

Intervention(s) in this Clinical Trial

• Drug: Pemetrexed
  • Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
• Dietary Supplement: Folic Acid
  • Folic Acid (350-1000 mcg) po qd; 5 doses during 7-day period preceding first dose of pemetrexed and dosing should continue during full course of therapy, and 21 days after last dose.
• Dietary Supplement: Vitamin B12
  • Vitamin B12 (1000ug) IM during week preceding first dose of pemetrexed and every 3 cycles thereafter.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle

Primary Measures

• · To determine the rates of best overall PSA response (≥ 50% decline in PSA) at any time during the study with single agent pemetrexed in subjects with HRPC whose disease has progressed following one prior taxane based chemotherapy regimen for HRPC·
  • Time Frame: 18 months
    Safety Issue?: No

Secondary Measures

• To determine time to disease progression, overall survival and duration of response (PSA criteria)
  • Time Frame: 18 months
    Safety Issue?: No
• To determine OBJECTIVE response per RECIST
  • Time Frame: 18 months
    Safety Issue?: No
• To determine the rate of clinical benefit (decreased pain, improved performance status)
  • Time Frame: 18 months
    Safety Issue?: No
• To determine the safety and tolerability of pemetrexed in subjects with HRPC whose disease has progressed following one prior taxane-based chemotherapy regimen for HRPC
  • Time Frame: 18 months
    Safety Issue?: Yes
• To explore whether polymorphisms of enzymes involved in pemetrexed metabolism impact its toxicity or efficacy profile
  • Time Frame: 18 months
    Safety Issue?: No

Inclusion Criteria:

• Histologically documented adenocarcinoma of the prostate
• Clinically refractory or resistant to hormone therapy as assessed by progression following at least one hormonal therapy (orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist)
• One prior taxane based chemotherapy regimen for HRPC
• Documented progression of disease after one taxane based prior chemotherapy regimen for HRPC. Progression is defined as at least one of the following:
• An increase in PSA > 50% over nadir value on prior Taxane-based therapy
• Progression of measurable disease as defined by RECIST
• Progression of bone disease as defined by the appearance of one or more new bone lesions or worsening symptoms
• Orchiectomy or testosterone levels < 50 ng/dL maintained by LHRH agonist
• Prior chemotherapy, or other experimental anticancer agents must be completed > 4 weeks prior to being registered for protocol therapy
• Palliative radiotherapy must be completed at least 14 days prior to registration.

Exclusion Criteria:

• Intravenous radio-isotopes therapy must be completed at least 6 weeks prior to registration
• No brain metastasis that are untreated and/or not controlled and/or still requiring corticosteroids
• No history of other malignancies within 5 years prior to being registered for protocol therapy, except for adequately treated basal or squamous cell skin cancer
• No history of uncontrolled psychiatric illness or serious systemic disease, including active infection, uncontrolled hypertension
• No surgery or significant traumatic injury within 21 days prior to being registered for protocol therapy
• Patients must be willing to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8 day period for long acting agents such as piroxicam)
• Patients must be willing to take folic acid or vitamin B12 supplementation

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hoosier Oncology Group

Overall Clinical Trial Officials and Contacts

Christopher Sweeney, M.B.B.S. Study Chair Hoosier Oncology Group, LLC  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00216099

Study ID Number: HOG GU03-67

ClinicalTrials.gov Identifier: NCT00216099

Health Authority: United States: Institutional Review Board

Hoosier Oncology Group Home Page