Study of Irofulven in Patients With Hormone-refractory Prostate Cancer - Full Text View

Sponsor:	Eisai Inc.
Information provided by:	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT00124566

Purpose

The purpose of this study is to assess the efficacy and safety of irofulven-based regimens compared to mitoxantrone plus prednisone in patients with hormone-refractory prostate cancer (HRPC) whose disease has progressed following Taxotere based regimens.

Condition	Intervention	Phase
Prostate Cancer	Drug: Irofulven + prednisone Drug: Irofulven + capecitabine + prednisone Drug: Mitoxantrone + prednisone	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Three-Arm Randomized Phase II Clinical Study of Irofulven/Prednisone, Irofulven/Capecitabine/Prednisone or Mitoxantrone/Prednisone in Docetaxel-Pretreated Hormone-Refractory Prostate Cancer Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Prednisone Mitoxantrone Mitoxantrone hydrochloride Docetaxel Capecitabine

U.S. FDA Resources

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:

Time to progression: RECIST (Response Evaluation Criteria in Solid Tumors) criteria [ Time Frame: Between randomization and study discontinuation or disease progression, whichever occurs later. ] [ Designated as safety issue: No ]
Time to progression: Prostate-specific antigen (PSA) evolution (Prostate-Specific Antigen Working Group Recommendations [PSAWGR criteria]). [ Time Frame: Between randomization and study discontinuation or disease progression, whichever occurs later. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Efficacy: Overall survival; objective response rate and PSA response rate according to RECIST and PSAWGR criteria, respectively. [ Time Frame: Between randomization and death. ] [ Designated as safety issue: No ]
Determine safety profile of each treatment arm: incidence and severity of adverse events (AEs), serious AEs, and laboratory abnormalities. [ Time Frame: Between randomization until a minimum of 30 days after last dose of study drug; treatment-related AEs will be followed until resolution. ] [ Designated as safety issue: Yes ]
Assess pain response in patients with significant pain at baseline using Tannock criteria and McGill-Melzack Pain Questionnaire. [ Time Frame: Seven days prior to randomization and prior to each new cycle of study drug administration. ] [ Designated as safety issue: No ]
Quality of life (QOL) as measured by the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI). [ Time Frame: Between baseline and study drug discontinuation. ] [ Designated as safety issue: No ]

Estimated Enrollment:	135
Study Start Date:	June 2004
Estimated Primary Completion Date:	March 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Irofulven + prednisone	Drug: Irofulven + prednisone Subjects will receive irofulven in a 30 minute intravenous (IV) infusion at a dose of 0.45 mg/kg on Days 1 and 8 every 3 weeks. Subjects will receive oral prednisone at a dose of 10 mg per day in the morning.
Experimental: 2 Irofulven + capecitabine + prednisone	Drug: Irofulven + capecitabine + prednisone Subjects will receive irofulven in a 30 minute intravenous (IV) infusion at a dose of 0.4 mg/kg on Days 1 and 15 every 4 weeks. Subjects will receive oral capecitabine at a dose of 1000 mg/m^2 twice daily for 15 days every 28 days. Subjects will receive oral prednisone at a dose of 10 mg per day in the morning.
Active Comparator: 3 Mitoxantrone + prednisone	Drug: Mitoxantrone + prednisone Subjects will receive mitoxantrone in an intravenous (IV) infusion (5 to 15 minutes) at a dose of 12 mg/m^2 per day, once every 3 weeks. Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning.

Detailed Description:

For every five patients randomized, two will receive treatment number 1 (irofulven + prednisone), two patients will receive treatment number 2 (irofulven + capecitabine (Xeloda®) + prednisone), and one patient will receive treatment number 3 (mitoxantrone + prednisone). This is not a blinded study, so both the patient and doctor will know which treatment has been assigned.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

To be included in the study, patients must meet the following criteria:

Cancer of the prostate confirmed by a biopsy sample.
18 years of age or older.
Disease must have spread beyond the prostate as proven by chest x ray, abdominal and pelvic computed tomography (CT) scan, bone scan or clinical examination.
At least one prior hormonal treatment with documented disease progression during hormone therapy.
One previous line of chemotherapy that included Taxotere® (as monotherapy or in combination). This could be in addition to estramustine single agent therapy.
Disease progression during prior Taxotere-based therapy or within 3 months of discontinuing.
Recovered from any toxic effects of prior chemotherapy, radiotherapy and surgery.
Recovered from any toxic effects associated with other investigational drugs, if applicable.
Signed informed consent obtained prior to initiation of any study-specific procedures or treatment.

Exclusion Criteria:

Patients cannot participate in the study if any of the following apply:

Unable to use prednisone.
Prior treatment with irofulven, capecitabine (Xeloda), continuous/protracted infusion 5-FU (5-fluorouracil) (infusion duration greater than or equal to 24 hours), other fluoropyrimidines or mitoxantrone.
Ongoing treatment with a corticosteroid at a prednisone-equivalent dose > 10 mg/day.
More than 1 prior treatment with either 153Sm or 89Sr, or radioisotope treatment within 8 weeks prior to entering this study.
Initiation of treatment with bisphosphonate agents (e.g., pamidronate, etidronate) within 2 months of entering the study. Pre-existing treatment with bisphosphonate agents is to be continued during this study.
Treatment with warfarin and/or phenytoin within 14 days before entering this study or during the study period.

Please note: There are additional inclusion/exclusion criteria. The study center will determine if patients meet all of the criteria. If patients do not qualify for the trial, study personnel will explain the reasons. If patients do qualify, study personnel will explain the trial in detail and answer any questions. Patients can then decide if they wish to participate.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124566

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Sponsors and Collaborators

Eisai Inc.

More Information

No publications provided

Responsible Party:	Eisai Medical Services, Eisai Inc.
ClinicalTrials.gov Identifier:	NCT00124566 History of Changes
Other Study ID Numbers:	IROF-018
Study First Received:	July 26, 2005
Last Updated:	August 27, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eisai Inc.:

Irofulven
Docetaxel
Taxotere

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Irofulven
Capecitabine
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents
Radiation-Sensitizing Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 24, 2012