Preoperative Docetaxel for Localized Progressive Castration-resistant Prostate Cancer (CRPC)

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Male

Summary

Objectives:

Primary:

• To evaluate the association of the probability of increase in phosphorylation of platelet-derived growth factor receptor (PDGFR) of > 0.5 in peripheral blood leucocytes following pre-operative docetaxel chemotherapy, with progression-free survival in localized castration-resistant prostate cancer (CRPC)

Secondary:

• To evaluate the association of the probability of increase in phosphorylated platelet-derived growth factor receptor (PDGFR) expression in peripheral blood leucocytes > 0.5 with indices of tumor regression including PSA-decline by 50% and measures of objective regression of tumor by transrectal MRI following pre-operative docetaxel therapy.

• Explore associations of probability of increase in phosphorylated PDGFR in peripheral blood leucocytes following pre-operative docetaxel therapy with plasma PDGF kinetics and spatial and quantitative PDGF and phosphorylated PDGFR expression in tumor and stromal compartments in resected specimens.

• Evaluate the association of probability of increase in phosphorylated PDGFR expression in peripheral blood leucocytes following pre-operative docetaxel chemotherapy with overall survival outcomes.

• Assess global quality of life measures at baseline and 6 and 12 months post-operatively.

• Create a tissue archive comprising tumor and peripheral blood specimens as a suitable resource for future genomic and proteomic studies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Sanofi
• Treatments: Docetaxel; Prednisone

Criteria

Inclusion Criteria:

1. Patients with adenocarcinoma of the prostate (ductal or acinar).

2. Symptomatic or evidence of progressive disease in the primary tumor by digital rectal examination, cystoscopy and/or radiological imaging without symptomatic or objective evidence of systemic disease progression.

3. Patients must have a castrate serum testosterone level (last six weeks. For patients who are medically castrated, luteinizing hormone releasing hormone analog must continue to maintain testicular suppression.

4. Patients on antiandrogens should be discontinued from flutamide, nilutamide or cyproterone acetate for at least 4 weeks and bicalutamide for 6 weeks. If localized progression is documented during or after this time interval, patients are eligible. Patients who have not had response to deferred (secondary) therapy with antiandrogens do not have to satisfy this waiting period prior to enrollment.

5. Surgically resectable disease as assessed by the collaborating urological oncologist.

6. Patients must be >/= 18 years of age.

7. Patients must have a performance status of

8. Patients must have an expected survival from cancer or co-morbidity of six months.

9. Patients will not receive any concurrent biological, immunological, second-line hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses of corticosteroid for non-malignant disease while disease progression was established may continue on such therapy.

10. Patients may not have received docetaxel or other chemotherapeutic agents in the last 6 months or have been defined as docetaxel-resistant or intolerant previously.

11. Patients must have adequate bone marrow function defined as an Hgb >/= 8.0 g/dl, absolute peripheral granulocyte count of >/= 1,500/mm^3 and platelet count of >/= 100,000/mm^3.

12. Patients must have adequate hepatic function defined with a bilirubin oflimits of normal. AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used (see chart below in Study Plan).

13. Patients must have adequate renal function defined as creatinine clearance >/= 30 cc/min (measured or calculated by Cockcroft and Gault formula).

14. Must be fully recovered from any previous surgery, in terms of wound healing.

15. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution.

16. Men with the ability to father a child must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

Exclusion Criteria:

1. Patients with severe or uncontrolled infection defined as symptomatic and/or requiring intravenous antibiotics.

2. Patients with small cell or sarcomatoid variant of prostate cancer.

3. Patients with symptomatic congestive heart failure (CHF), pulmonary embolus, vascular thrombosis, transient ischemic attack, cerebrovascular accident, unstable angina or MI in the last 6 months or evidence of active myocardial ischemia by symptoms or ECG.

4. Oxygen-dependent lung disease, > grade 2 peripheral neuropathy, uncontrolled hypertension or uncontrolled diabetes mellitus.

5. Active second malignancies. Non-threatening second malignancies such as superficial low-grade transitional cell carcinoma of the bladder, Rai Stage 0 chronic lymphocytic leukemia or stable small renal cell carcinomas may be exempt from such stipulation at the discretion of the Principal Investigator.

6. Patients who are unwilling to provide blood or tissue specimens required for the primary objectives of the study.

7. Overt psychosis or mental disability or otherwise incompetent to give informed consent. Patients with a history of non-compliance with medical regimens or who are considered potentially unreliable.

8. Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.