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

Alternate Title

Paclitaxel Poliglumex and Estradiol in Treating Patients With Stage IV Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Temporarily closed 18 and over NCI OHSU-2656 SOL-06048-L, NCT00459810

Objectives

Primary

1. Determine the PSA response rate in patients with androgen independent metastatic prostate cancer treated with paclitaxel poliglumex and transdermal estradiol.

Secondary

1. Determine the toxicity of this regimen in these patients.
2. Determine the response rate in patients treated with this regimen.
3. Determine the time to PSA progression and measurable disease progression in patients treated with this regimen.
4. Determine time to death from all causes in patients treated with this regimen.
5. Correlate levels of serum estradiol, serum cathepsin B, and bone turnover markers with PSA response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate
  • Stage IV disease
    • Radiographic evidence of regional or distant metastases



• Evidence of disease progression (by PSA and/or imaging studies) despite standard hormonal therapy and after exposure to docetaxel-containing chemotherapy, as evidenced by any of the following:
  • Measurable or evaluable disease progression, defined as the appearance of new lesion(s) or unequivocal increase in previously existing lesions or masses
  • Disease progression by PSA*, defined by 1 of the following:
    • 3 consecutively rising PSA with the second PSA taken ≥ 1 week after the first PSA
    • 2 consecutively rising PSA with a fourth PSA > the second PSA

   [Note: *The last required PSA must be after the required antiandrogen washout period for patients who have been on antiandrogen therapy]




• Must have received prior therapy with at least two 3-weekly doses or six weekly doses of docetaxel
  • Patients may have discontinued therapy due to progression, intolerance, completion of planned therapy, or other reasons
  • Prior treatment with combinations of docetaxel with estramustine phosphate sodium or noncytotoxic agents (biologic agents) allowed



• Serum testosterone < 50 ng/dL (unless surgically castrate)
  • Patients must continue androgen deprivation with a luteinizing hormone-releasing hormone agonist if they have not undergone orchiectomy



• No known or suspected brain metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• At least 6 weeks since prior antiandrogen therapy (4 weeks for flutamide)
  • No current evidence of an antiandrogen withdrawal response
• More than 4 weeks since prior radiotherapy
• More than 8 weeks since prior radiopharmaceutical therapy (strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium)
• No prior paclitaxel
• No other concurrent cytotoxic agents
• No other concurrent chemotherapy or biologic response modifiers
• No concurrent supplements known or suspected to contain supplemental estrogens

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN
• No other active malignancy except adequately treated nonmelanoma skin cancer or other noninvasive or in situ neoplasm
• No other significant active medical illness or infection that would preclude study compliance
• No significant cardiovascular illness, including any of the following:
  • NYHA class III or IV congestive heart failure
  • Unstable angina
  • Myocardial infarction within the past 6 months
  • Acute deep venous thrombosis
  • Acute pulmonary embolism
• No significant peripheral neuropathy ≥ grade 2

Expected Enrollment

A total of 50 patients will be accrued for this study.

Outcomes

PSA response rate

Toxicity
Response rate
Time to PSA progression and measurable disease progression
Time to death
Correlation of levels of serum estradiol, serum cathepsin B, and bone turnover markers with PSA response

Outline

This is a multicenter study.

Patients receive transdermal estradiol continuously (patches changed every 7 days) until the PSA level rises. Patients whose PSA increases above baseline or PSA decreases < 10% after 4 weeks of estradiol therapy or whose serum PSA reduction is < 50% after 12 weeks of estradiol therapy also receive paclitaxel poliglumex therapy. These patients receive paclitaxel poliglumex IV over 10-20 minutes on day 1. Treatment with paclitaxel poliglumex repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 6 months.

Trial Contact Information

Trial Lead Organizations

Oregon Health and Science University Cancer Institute

Tomasz Beer, MD, Principal investigator		Ph: 503-494-3253; 800-494-1234

Registry Information
Official Title		A Phase II Study of Paclitaxel Poliglumex (PPX) in Combination with Transdermal Estradiol for the Treatment of Androgen Independent Prostate Cancer After Docetaxel Chemotherapy
Trial Start Date		2007-02-28
Trial Completion Date		2010-02-28 (estimated)
Registered in ClinicalTrials.gov		NCT00459810
Date Submitted to PDQ		2007-03-09
Information Last Verified		2008-08-26
NCI Grant/Contract Number		CA69533