Study of Irofulven in Patients With Hormone-refractory Prostate Cancer

Sponsor

Eisai Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00124566

Collaborator

(none)

135

Enrollment

Locations

Arms

Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Irofulven Drug: Prednisone Drug: Mitoxantrone Drug: Capecitabine Drug: Irofulven	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Jun 1, 2004

Actual Primary Completion Date :

Jan 1, 2006

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Irofulven + prednisone	Drug: Irofulven 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. Drug: Prednisone Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning.
Experimental: 2 Irofulven + capecitabine + prednisone	Drug: Prednisone Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning. Drug: Capecitabine Subjects will receive oral capecitabine at a dose of 1000 mg/m^2 twice daily for 15 days every 28 days. Drug: Irofulven 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.
Active Comparator: 3 Mitoxantrone + prednisone	Drug: Prednisone Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning. Drug: Mitoxantrone 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.

Arm

Intervention/Treatment

Experimental: 1

Irofulven + prednisone

Drug: Irofulven

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.

Drug: Prednisone

Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning.

Experimental: 2

Irofulven + capecitabine + prednisone

Drug: Prednisone

Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning.

Drug: Capecitabine

Subjects will receive oral capecitabine at a dose of 1000 mg/m^2 twice daily for 15 days every 28 days.

Drug: Irofulven

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.

Active Comparator: 3

Mitoxantrone + prednisone

Drug: Prednisone

Subjects will also receive oral prednisone at a dose of 10 mg per day in the morning.

Drug: Mitoxantrone

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.

Outcome Measures

Primary Outcome Measures

Time to progression: RECIST (Response Evaluation Criteria in Solid Tumors) criteria [Between randomization and study discontinuation or disease progression, whichever occurs later.]
Time to progression: Prostate-specific antigen (PSA) evolution (Prostate-Specific Antigen Working Group Recommendations [PSAWGR criteria]). [Between randomization and study discontinuation or disease progression, whichever occurs later.]

Secondary Outcome Measures

Efficacy: Overall survival; objective response rate and PSA response rate according to RECIST and PSAWGR criteria, respectively. [Between randomization and death.]
Determine safety profile of each treatment arm: incidence and severity of adverse events (AEs), serious AEs, and laboratory abnormalities. [Between randomization until a minimum of 30 days after last dose of study drug; treatment-related AEs will be followed until resolution.]
Assess pain response in patients with significant pain at baseline using Tannock criteria and McGill-Melzack Pain Questionnaire. [Seven days prior to randomization and prior to each new cycle of study drug administration.]
Quality of life (QOL) as measured by the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI). [Between baseline and study drug discontinuation.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Locations

	City	State	Country
1	Hot Springs	Arkansas	United States
2	Jonesboro	Arkansas	United States
3	Greenbrae	California	United States
4	Colorado Springs	Colorado	United States
5	Bonita Springs	Florida	United States
6	Bradenton	Florida	United States
7	Cape Coral	Florida	United States
8	Ft. Meyers	Florida	United States
9	Naples	Florida	United States
10	Port Charlotte	Florida	United States
11	Sarasota	Florida	United States
12	Venice	Florida	United States
13	Atlanta	Georgia	United States
14	Augusta	Georgia	United States
15	Macon	Georgia	United States
16	Marietta	Georgia	United States
17	Chicago	Illinois	United States
18	Minneapolis	Minnesota	United States
19	Billings	Montana	United States
20	Albany	New York	United States
21	East Setauket	New York	United States
22	Kettering	Ohio	United States
23	Greenville	South Carolina	United States
24	Nashville	Tennessee	United States
25	Dallas	Texas	United States
26	Ft. Worth	Texas	United States
27	Tyler	Texas	United States
28	Spokane	Washington	United States
29	Marshfield	Wisconsin	United States
30	Belo Horizonte		Brazil
31	Porto Alegre		Brazil
32	Rio de Janeiro		Brazil
33	Calgary	Alberta	Canada
34	Vancouver	British Columbia	Canada
35	Winnipeg	Manitoba	Canada
36	London	Ontario	Canada
37	Montreal	Quebec	Canada
38	Santiago		Chile
39	Zagreb		Croatia
40	Avignon		France
41	Orleans		France
42	Paris		France
43	Saint-Brieuc		France
44	Saint-Gregoire		France
45	Lima		Peru
46	Bucharest		Romania
47	Cluj-Napoca		Romania
48	Arkhangelsk		Russian Federation
49	Chelyabinsk		Russian Federation
50	Moscow		Russian Federation