Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer
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.
Dietary Supplement: Folic Acid
Dietary Supplement: Vitamin B12
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Pemetrexed (Alimta) as Second-Line Therapy for Hormone Refractory Prostate Cancer: Hoosier Oncology Group GU03-67|
- Best Overall PSA Response [ Time Frame: Start of treatment until disease progression/recurrence (for life) ]
Best overall Prostate-Specific Antigen (PSA) response
PSA response is defined by a greater than or equal to 50% decline in PSA confirmed by a second PSA value at least 4 weeks after the first PSA response timepoint PSA Stable Disease is defined as less than a 50% decline in PSA and less than a 50% increase in PSA from baseline PSA progression is defined as greater than or equal to a 50% increase in PSA compared to baseline
- Overall Survival [ Time Frame: From study enrollment until death (for life) ]
- OBJECTIVE Overall Response Rate [ Time Frame: Start of treatment until disease progression/recurrence (for life) ]
Response Evaluation Criteria in Solid Tumors (RECIST). Objective overall response rate is defined as Complete Response (CR) + Partial Response (PR)
CR= Disappearance of all target and non-target lesions and normalization of tumor marker level PR= Disappearance of all target lesions and persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits OR at least a 30% decrease in the sum of the longest diameter, taking as reference the baseline sum longest diameter and disappearance of all non-target lesions or persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits
- Rate of Clinical Benefit [ Time Frame: Any time among evaluable subjects (for life) ]
A clinical benefit is defined as an improvement for at least 3 consecutive weeks in at least one of the following parameters without any sustained worsening in any other:
> 50% reduction in analgesic consumption or > 50% reduction in pain intensity or > 20 point gain in performance status.
- Safety and Tolerability [ Time Frame: 18 months ]Safety and Tolerability was evaluated by reporting the percentage of patient who experienced grade 3 or 4 toxicities using Common Terminology Criteria for Adverse Events CTCAE v3.0 criteria. CTCAE grades the severity of an adverse event from 1-5 where 1=least severe and 5=death.
- RFC1 G80A Genotype [ Time Frame: Screening ]Samples for RFC1 G80A pharmacogenetic analysis were collected at screening
- Time to Progression [ Time Frame: Study enrollment until progression per RECIST or PSA (for life) ]Progression per Response Evaluation Criteria in Solid Tumors (RECIST) or Prostate-Specific Antigen (PSA) Progression RECIST PD=at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions PSA progression=increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline *Note, upper confidence interval was not reached*
- Time to Prostate-Specific Antigen (PSA)/Serological Progression [ Time Frame: From study enrollment to progression per PSA criteria (for life) ]Serological Progression (sPD) - increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline
|Study Start Date:||February 2005|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Experimental: Investigational Treatment
Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Other Name: AlimtaDietary Supplement: Folic Acid
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.Dietary Supplement: Vitamin B12
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.
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
- Absolute Neutrophil Count (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 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.
- Calculated creatinine clearance >45 mL/min based on the standard Cockroft and Gault formula
- 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
- Not specified
Please refer to this study by its ClinicalTrials.gov identifier: NCT00216099
|United States, Illinois|
|Medical & Surgical Specialists, LLC|
|Galesburg, Illinois, United States, 61401|
|United States, Indiana|
|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|
|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|
|Study Chair:||Christopher Sweeney, M.B.B.S.||Hoosier Oncology Group, LLC|