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

Condition(s) targeted: Prostate Cancer

Intervention: paclitaxel poliglumex (Drug); therapeutic estradiol (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Oregon Health and Science University Cancer Institute

Official(s) and/or principal investigator(s):
Tomasz M. Beer, MD, Principal Investigator, Affiliation: Oregon Health and Science University Cancer Institute

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.

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

Study design: Treatment, Open Label

Primary outcome: PSA response rate

Secondary outcome:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

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

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Oregon Health and Science University Cancer Institute, Portland, Oregon 97239-3098, United States; Recruiting
Tomasz M. Beer, MD, Phone: 503-494-0365

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

Starting date: February 2007
Last updated: July 23, 2008