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A Phase II Study of Paclitaxel Poliglumex (PPX) in Combination With Transdermal Estradiol for the Treatment of Androgen Independent Prostate Cancer After Docetaxel Chemotherapy


Phase 2
18 Years
N/A
Not Enrolling
Male
Prostate Cancer

Thank you

Trial Information

A Phase II Study of Paclitaxel Poliglumex (PPX) in Combination With Transdermal Estradiol for the Treatment of Androgen Independent Prostate Cancer After Docetaxel Chemotherapy


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Prostate Specific Antigen (PSA) Response Rate: Number of Subjects With Decreases in PSA of at Least 50%

Outcome Description:

PSA response rate is defined at the number of patients who experienced a PSA decline of equal to or greater than 50%, confirmed by a second measurement at least 4 weeks later.

Outcome Time Frame:

While receiving study agents (on average, 3 months)

Safety Issue:

No

Principal Investigator

Tomasz M. Beer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000540438

NCT ID:

NCT00459810

Start Date:

February 2007

Completion Date:

July 2009

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms

Name

Location

UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
OHSU Knight Cancer InstitutePortland, Oregon  97239