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”

RATIONALE: Drugs used in chemotherapy, such as paclitaxel poliglumex, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Estradiol may kill prostate cancer cells that no longer respond to hormone therapy.

Giving paclitaxel poliglumex together with estradiol may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving paclitaxel poliglumex together with estradiol works in treating patients with stage IV prostate cancer.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: February 2010

OBJECTIVES:

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

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

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.

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

Intervention(s) in this Clinical Trial

• Drug: paclitaxel poliglumex
• Drug: therapeutic estradiol

Primary Measures

• PSA response rate
  • Safety Issue?: No

Secondary Measures

• Toxicity
  • Safety Issue?: Yes
• Response rate
  • Safety Issue?: No
• Time to PSA progression and measurable disease progression
  • Safety Issue?: No
• Time to death
  • Safety Issue?: No
• Correlation of levels of serum estradiol, serum cathepsin B, and bone turnover markers with PSA response
  • Safety Issue?: No

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

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

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Oregon Health and Science University Cancer Institute

Overall Clinical Trial Officials and Contacts

Tomasz M. Beer, MD Principal Investigator Oregon Health and Science University Cancer Institute  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00459810

Study ID Number: CDR0000540438

ClinicalTrials.gov Identifier: NCT00459810

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database