Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Pemetrexed; Folic Acid; Vitamin B12
Intervention description: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle; 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.; 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.
Intervention MeSH terms: Folic Acid; Vitamin B 12; Hydroxocobalamin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer

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.
    

Eligibility criteria:

        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