Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer

This study has been completed.
Eli Lilly and Company
Walther Cancer Institute
Information provided by:
Hoosier Cancer Research Network Identifier:
First received: September 12, 2005
Last updated: April 27, 2011
Last verified: April 2011

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.

Condition Intervention Phase
Prostate Cancer
Drug: Pemetrexed
Dietary Supplement: Folic Acid
Dietary Supplement: Vitamin B12
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II Study of Pemetrexed (Alimta) as Second-Line Therapy for Hormone Refractory Prostate Cancer: Hoosier Oncology Group GU03-67

Resource links provided by NLM:

Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine time to disease progression, overall survival and duration of response (PSA criteria) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To determine OBJECTIVE response per RECIST [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To determine the rate of clinical benefit (decreased pain, improved performance status) [ Time Frame: 18 months ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
  • To explore whether polymorphisms of enzymes involved in pemetrexed metabolism impact its toxicity or efficacy profile [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: February 2005
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
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.

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


  • ANC > 1500/mm3
  • Platelet count > 100,000/mm3
  • Hemoglobin > 9 g/dL


  • 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.


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


  • 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


  • Not specified

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00216099

United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Elkhart Clinic
Elkhart, Indiana, United States, 46515
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, United States, 46202
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
AP&S Clinic
Terre Haute, Indiana, United States, 47804
United States, Michigan
Center for Hematology/Oncology of S. Michigan
Jackson, Michigan, United States, 49201
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hematology Oncology Associates S.J., P.A.
Mt. Holly, New Jersey, United States, 08060
United States, Pennsylvania
Consultants in Medical Oncology & Hematology
Drexel Hill, Pennsylvania, United States, 19026
Pennsylvania Oncology-Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Sponsors and Collaborators
Hoosier Cancer Research Network
Eli Lilly and Company
Walther Cancer Institute
Study Chair: Christopher Sweeney, M.B.B.S. Hoosier Oncology Group, LLC
  More Information

Additional Information:
Responsible Party: Christopher Sweeney, M.B., B.S., Hoosier Oncology Group Identifier: NCT00216099     History of Changes
Other Study ID Numbers: HOG GU03-67 
Study First Received: September 12, 2005
Last Updated: April 27, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Hoosier Cancer Research Network:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Folic Acid
Vitamin B 12
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Hematinics processed this record on July 26, 2016