Clinical trial NCT00216099: Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer
Official title: A Phase II Study of Pemetrexed (Alimta) as Second-Line Therapy for Hormone Refractory Prostate Cancer: Hoosier Oncology Group GU03-67
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: Walther Cancer Institute
First posted: 2005-09-22
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Best Overall PSA Response
timeFrame: Start of treatment until disease progression/recurrence (for life)
Secondary outcomes:
measure: Overall Survival
timeFrame: From study enrollment until death (for life)
measure: OBJECTIVE Overall Response Rate
timeFrame: Start of treatment until disease progression/recurrence (for life)
measure: Rate of Clinical Benefit
timeFrame: Any time among evaluable subjects (for life)
measure: Safety and Tolerability
timeFrame: 18 months
measure: RFC1 G80A Genotype
timeFrame: Screening
measure: Time to Progression
timeFrame: Study enrollment until progression per RECIST or PSA (for life)
measure: Time to Prostate-Specific Antigen (PSA)/Serological Progression
timeFrame: From study enrollment to progression per PSA criteria (for life)
Other outcomes:
Locations:
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Quality Cancer Center (MCGOP)
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Terre Haute
country: United States
facility: AP&S Clinic
state: Indiana
city: Jackson
country: United States
facility: Center for Hematology/Oncology of S. Michigan
state: Michigan
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Mt. Holly
country: United States
facility: Hematology Oncology Associates S.J., P.A.
state: New Jersey
city: Drexel Hill
country: United States
facility: Consultants in Medical Oncology & Hematology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology-Hematology Associates
state: Pennsylvania
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Christopher Sweeney, M.B.B.S.
role: STUDY_CHAIR
References:
citation: Hahn NM, Zon RT, Yu M, Ademuyiwa FO, Jones T, Dugan W, Whalen C, Shanmugam R, Skaar T, Sweeney CJ. A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67. Ann Oncol. 2009 Dec;20(12):1971-6. doi: 10.1093/annonc/mdp244. Epub 2009 Jul 15.