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

This study has been completed.
Sponsor:
Collaborators:
Eli Lilly and Company
Walther Cancer Institute
Information provided by (Responsible Party):
Christopher Sweeney, MBBS, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00216099
First received: September 12, 2005
Last updated: June 18, 2016
Last verified: June 2016
  Purpose

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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Best Overall PSA Response [ Time Frame: Start of treatment until disease progression/recurrence (for life) ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From study enrollment until death (for life) ] [ Designated as safety issue: No ]
  • OBJECTIVE Overall Response Rate [ Time Frame: Start of treatment until disease progression/recurrence (for life) ] [ Designated as safety issue: No ]

    Response Evaluation Criteria in Solid Tumors (RECIST). Objective overall response rate is defined as Complete Response (CR) + Partial Response (PR)

    Per RECIST:

    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) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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


Enrollment: 49
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
Experimental: Investigational Treatment
  • Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
  • Oral Folic Acid, once per day for 7 days preceding pemetrexed dose, continued daily, and for 21 days after the last dose of pemetrexed.
  • Vitamin B12, 1000ug intramuscular injection 7 days preceding pemetrexed dose, and every three cycles thereafter on the same day of pemetrexed administration
Drug: Pemetrexed
Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Other Name: Alimta
Dietary 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.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00216099

Locations
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
Christopher Sweeney, MBBS
Eli Lilly and Company
Walther Cancer Institute
Investigators
Study Chair: Christopher Sweeney, M.B.B.S. Hoosier Oncology Group, LLC
  More Information

Additional Information:
Publications:
Responsible Party: Christopher Sweeney, MBBS, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00216099     History of Changes
Other Study ID Numbers: HOG GU03-67 
Study First Received: September 12, 2005
Results First Received: December 17, 2015
Last Updated: June 18, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Hoosier Cancer Research Network:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Vitamins
Folic Acid
Vitamin B 12
Hydroxocobalamin
Hormones
Vitamin B Complex
Pemetrexed
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hematinics
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016