Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and estramustine, work in different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of prostate cancer by stopping blood flow to the tumor. Combining thalidomide with chemotherapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining paclitaxel and estramustine with thalidomide in treating patients who have progressive metastatic androgen-independent prostate cancer.

Further Study Information

OBJECTIVES:

• Determine the maximum tolerated dose of paclitaxel and thalidomide administered with estramustine in patients with progressive metastatic androgen-independent prostate cancer.

• Determine the efficacy of this regimen in these patients.

• Determine the objective response rate and prostate-specific antigen response rate in patients treated with this regimen.

• Determine time to disease progression, performance status, analgesic consumption, and survival of patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a phase I dose-escalation study of paclitaxel and thalidomide followed by a phase II study.

• Phase I: Patients receive oral estramustine three times daily on days 1-5 and 8-12, oral thalidomide once daily on days 1-21, and paclitaxel IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

• Phase II: Patients receive paclitaxel, estramustine, and thalidomide as in arm I at the MTD.

PROJECTED ACCRUAL: A total of 48-75 patients (18 for phase I and 30-57 for phase II) will be accrued for this study within 8-15 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma* of the prostate

• Biopsy of a metastatic site allowed provided the tissue stains positive for prostate-specific antigen (PSA)

• Indicator lesions need not be biopsy proven if the clinical presentation is characteristic

• Nodal and/or visceral disease allowed NOTE: *Variant histologies (e.g., ductal carcinoma and small cell carcinoma) are allowed only for the phase I portion of the study

• Progressive androgen-independent disease, as evidenced by the following:

• Testosterone ≤ 50 ng/dL OR prior bilateral orchiectomy

• Patients must continue luteinizing hormone-releasing hormone agonists to maintain castrate levels

• Symptomatic progression OR rising PSA on two occasions, at least 1 week apart, with a minimum pretreatment PSA of 5 ng/mL

• Progressive disease after at least 1, but no more than 2, prior chemotherapy regimens for prostate cancer in the neoadjuvant or metastatic setting (phase II only)

• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

Hepatic

• SGOT and SGPT < 2 times upper limit of normal (ULN)

• Bilirubin < 2 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL OR

• Creatinine clearance ≥ 35 mL/min

Cardiovascular

• No clinical history of heart disease

• ECG normal OR

• Ejection fraction ≥ 45% by echocardiogram, MUGA, or ventriculography

Other

• No active or uncontrolled infection

• No significant psychiatric disorder that would preclude giving informed consent

• No grade 2 or greater peripheral neuropathy

• No other malignancy within the past 5 years except superficial bladder cancer or basal cell skin cancer

• No other serious medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior immunotherapy AND evidence of disease progression

• More than 2 weeks since prior antiangiogenesis therapy AND evidence of disease progression

Chemotherapy

• See Disease Characteristics

• No more than 2 prior chemotherapy* regimens for prostate cancer

• More than 3 weeks since prior chemotherapy and recovered

• Prior taxanes allowed NOTE: *Ketoconazole is considered chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 4 weeks since prior flutamide or nilutamide (6 weeks for bicalutamide) AND no evidence of response or disease progression since withdrawal

• No concurrent antiandrogens (e.g., flutamide, nilutamide or bicalutamide)

Radiotherapy

• More than 12 weeks since prior strontium chloride Sr 89

• No more than 1 prior dose of strontium chloride Sr 89

• More than 3 weeks since prior radiotherapy

• No prior radiotherapy to more than 15% of the bone marrow

Surgery

• See Disease Characteristics

• At least 2 weeks since prior surgery

Other

• More than 2 weeks since prior non-androgen mediated pathway therapy (e.g., epidermal growth factor receptor antagonists or farnesyl transferase inhibitors) AND evidence of disease progression

• More than 2 weeks since prior herbal or alternative medicines or PC-SPES AND evidence of disease progression

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Danai Daliani

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00082693
Information obtained from ClinicalTrials.gov on December 14, 2011

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