Ixabepilone With or Without Estramustine in Treating Patients With Progressive Prostate Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00025194

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as ixabepilone and estramustine, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether BMS-247550 is more effective with or without estramustine in treating prostate cancer.

PURPOSE: This randomized phase I/II trial is studying the best dose of ixabepilone when given together with estramustine and to see how well giving ixabepilone together with estramustine works compared to ixabepilone alone in treating patients with progressive prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: estramustine phosphate sodium Drug: ixabepilone	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of ixabepilone combined with estramustine in patients with progressive androgen-independent adenocarcinoma of the prostate. (Phase I)
Compare the safety and efficacy of ixabepilone with or without estramustine in this patient population. (Phase II)
Correlate the clinical outcomes with reverse transcriptase-polymerase chain reaction-based assay for prostate-specific antigen mRNA in patients treated with these regimens.

OUTLINE: This is a dose-escalation study of ixabepilone (phase I) followed by a randomized, multicenter study (phase II).

Phase I: Patients receive ixabepilone IV over 3 hours on day 2 and oral estramustine 3 times daily on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive ixabepilone IV over 3 hours at the MTD on day 2 and estramustine as in phase I.
Arm II: Patients receive ixabepilone IV over 3 hours at the MTD on day 1. Treatment in both arms repeats as in phase I.

Patients are followed every 12 weeks until disease progression.

PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of this study and a total of 44-92 patients (22-46 per treatment arm) will be accrued for phase II of this study within 12-18 months.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase I And Randomized Phase 2 Trial Of Epothilone B Analogue BMS 247550 (NSC # 710428) Administered Every 21 Days With Or Without Oral Estramustine Phosphate In Patients With Androgen Independent Prostate Cancer

Study Start Date :

Jul 1, 2001

Actual Study Completion Date :

Jul 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the prostate
Must have disease progression meeting 1 of the following criteria:
Rising prostate-specific antigen (PSA) on at least 3 consecutive measurements taken more than 1 week apart
Measurable disease, defined as new or progressive soft tissue masses on CT scan or MRI
New metastatic lesions by radionuclide bone scan
The most recent PSA must be at least 4 ng/mL if no measurable disease is present
Ineligible if sole manifestation of progressive disease is an increase in disease-related symptoms
Serum testosterone no greater than 50 ng/mL
One of the following therapies for maintenance of castrate status required:
Must continue on gonadotropin-releasing hormone analogs (e.g., leuprolide or goserelin) to maintain castrate levels of serum testosterone
Developed disease progression after discontinuation of the antiandrogen that was part of the first-line hormonal therapy
Prior surgical orchiectomy
Developed disease progression after discontinuation of megestrol
No known brain metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 70-100%

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No history of bleeding disorder that would preclude anticoagulation with warfarin

Hepatic:

Bilirubin normal
AST/ALT no greater than 2.5 times upper limit of normal (ULN)
PT/PTT normal (unless anticoagulated for other reasons [e.g., atrial fibrillation])

Renal:

Creatinine no greater than 1.5 times ULN

Cardiovascular:

No significant cardiovascular disease
No symptomatic congestive heart failure
No New York Heart Association class III or IV heart disease
No active unstable angina pectoris
No cardiac arrhythmia
No myocardial infarction within the past 6 months
No history of hemorrhagic or thrombotic cerebrovascular accident or deep venous thrombosis within the past 6 months

Pulmonary:

No pulmonary embolism within the past 6 months

Other:

Fertile patients must use effective contraception
No history of allergic reactions to compounds of similar chemical or biological composition to the epothilones
No history of recent gastrointestinal bleeding that would preclude anticoagulation with warfarin
No other concurrent active malignancy except nonmelanomatous skin cancer
Disease not considered currently active if completely treated with less than a 30% risk for relapse
No other concurrent uncontrolled illness
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF) except for neutropenic fever
No concurrent immunotherapy

Chemotherapy:

No prior chemotherapy
No other concurrent chemotherapy

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

No prior palliative radiotherapy to more than 25% of bone marrow
No prior radioisotope therapy with strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
No concurrent therapeutic radiotherapy
Concurrent focal radiotherapy for palliation of bone disease-related symptoms allowed at the investigator's discretion

Surgery:

See Disease Characteristics
At least 4 weeks since prior major surgery

Other:

No other concurrent anticancer investigational or commercial agents or therapies
No concurrent herbal, alternative, or food supplements (e.g., PC-SPES, saw palmetto, or St. John's Wort)
No concurrent combination antiretroviral therapy for HIV-positive patients
No initiation of bisphosphonates immediately before or during study
Concurrent bisphosphonates allowed if developed disease progression while on stable doses
Concurrent daily multivitamin allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
4	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021