Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Paclitaxel, Estramustine, and Thalidomide in Treating Patients With Progressive Metastatic Androgen-Independent Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI	MDA-ID-00087 NCT00082693

Special Category: SPORE trial

Objectives

1. Determine the maximum tolerated dose of paclitaxel and thalidomide administered with estramustine in patients with progressive metastatic androgen-independent prostate cancer.
2. Determine the efficacy of this regimen in these patients.
3. Determine the objective response rate and prostate-specific antigen response rate in patients treated with this regimen.
4. Determine time to disease progression, performance status, analgesic consumption, and survival of patients treated with this regimen.
5. Determine the toxicity of this regimen in these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Danai Daliani, Protocol chair(Contact information may not be current)		Ph: 713-792-2830; 800-392-1611

Registry Information
Official Title		Phase I/II Study of Paclitaxel, Estramustine Phosphate and Thalidomide for Patients with Metastatic Androgen-Independent Prostate Carcinoma (Al-PCa)
Trial Start Date		2001-03-04
Registered in ClinicalTrials.gov		NCT00082693
Date Submitted to PDQ		2003-10-20
Information Last Verified		2004-04-26
NCI Grant/Contract Number		P30-CA16672, P50-CA90270

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