Clinical trial NCT00176527: Isotretinoin, Interferon Alfa-2b, Docetaxel, and Estramustine in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
Official title: A Phase II Trial of 13-Cis Retinoic Acid, Alpha Interferon, Taxotere, and Estramustine (R.I.T.E.) for the Treatment of Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: recurrent prostate cancer
stage IV prostate cancer
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-15
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Isotretinoin may help prostate cancer cells become more like normal cells, and to grow and spread more slowly. Interferon alfa-2b may interfere with the growth of tumor cells. Drugs used in chemotherapy, such as docetaxel and estramustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving isotretinoin and interferon alfa-2b together with docetaxel and estramustine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving isotretinoin and interferon alfa-2b together with docetaxel and estramustine works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate, in terms of change in measurable disease or prostate-specific antigen levels, in patients with hormone-refractory metastatic prostate cancer treated with isotretinoin, recombinant interferon alfa-2b, docetaxel, and estramustine phosphate sodium.

Secondary

* Determine the effect of this regimen on bcl-2 family proteins in peripheral blood mononuclear cell samples obtained from these patients.

OUTLINE: Patients receive oral isotretinoin once daily on days 1-4, recombinant interferon alfa-2b subcutaneously once daily on days 1-4, oral estramustine phosphate sodium three times daily on days 1-5, and docetaxel IV over 1 hour on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Peripheral blood mononuclear cells are acquired via blood draw at baseline and on days 2, 3, or 4 and analyzed for bcl-2 protein by IHC and electrophoresis.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed hormone-refractory metastatic prostate cancer

  * Patients who have been recently withdrawn from treatment with bicalutamide or flutamide must demonstrate progression of disease
* Measurable disease OR prostate-specific antigen level ≥ 10 ng/mL

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Estimated life expectancy ≥ 6 months
* Absolute neutrophil count ≥ 1,500/mm³
* Hemoglobin ≥ 8 g/dL
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
* Bilirubin normal
* AST, ALT, and alkaline phosphatase (AP) must meet 1 of the following criteria:

  * AP normal and AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  * AP elevated and AST and ALT normal
* No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
* No peripheral neuropathy \> grade 1
* No concurrent active infections
* No concurrent major depression or suicidal ideation
* No concurrent medical condition that would preclude study participation
* No known HIV positivity
* Fertile patients must use effective contraception during and for 10 weeks after completion of study therapy

PRIOR CONCURRENT THERAPY:

* Recovered from prior surgery or radiotherapy
* No prior chemotherapy, retinoids, or interferon therapy
* More than 4 weeks since prior flutamide
* More than 6 weeks since prior bicalutamide

Primary outcomes:
measure: Response (biochemical and measurable disease)
measure: Bcl-2 modulation in peripheral blood mononuclear cells
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Robert S. DiPaola, MD
role: PRINCIPAL_INVESTIGATOR
References: