Hormone refractory prostate cancer with painful bone metastases MedDRA version: 8.1 Level: LLT Classification code 10036909 Term: Prostate cancer metastatic
Conditions
Sponsors
University Medical center Utrecht
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Related to prostate cancer: 1. Histologically documented adenocarcinoma of the prostate. 2. Presence of more than one osteoblastic bone metastasis confirmed by 99mTc-labeled bisphosphonates bone scan performed within 8 weeks prior to study entry. 3. Bone pain and/or painmedication. 4. Clinically progressive hormone refractory disease, as documented by one or more of the following: a. Two documented consecutive increases in total PSA over a previous reference value (first increase at least one week after reference value). Increased total PSA level must be at least 5 µg/L. b. New lesion on bone scan (progressive measurable disease). c. Increase in bidimensionally measurable disease. 5. Karnofsky performance status ³ 60% (Appendix III). 6. Life expectancy of at least 3 months. 7. Patients with lower urinary tract obstruction or incontinence must consent to catheterization of the bladder for up to 6 hours after administration of Re-188-HEDP . Related to previous or concomitant therapies: 8. Patients receiving anti-androgen treatment can either stop or continue their treatment. Patients who stop anti-androgens must demonstrate no decrease in total PSA values on at least two occasions at least 1 week apart after anti-androgen withdrawal. Flutamide must be discontinued for 4 weeks, and bicalutamide, megestrol acetate, cyproterone acetate, or nilutamide must be discontinued for at least 6 weeks prior to study entry. Patients who continue anti-androgen treatment must go on with their treatment during the whole study period. 9. Patients under LH-RH agonists must continue their treatment. Related to the patient: 10. Age ³ 18 years. 11. Ability to understand and willingness to sign a written informed consent document. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Related to prostate cancer: 1. Patients with pathologic long-bone fractures (unless surgically stabilized), imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or clinical evident spinal cord compression. 2. Patient known to have a malignancy other than prostate cancer (but not including basal cell carcinoma of the skin). Related to previous or concomitant therapies: 3. Previous chemotherapy (including Estramustine) within 6 weeks prior to screening. 4. Any other medicine taken with the intension to treat the disease (except LH-RH agonist). 5. Use of Interferon-alpha, Allopurinol, Sorivudine and analogues and Folinic acid. 6. Prior treatment with a systemic radiotherapeutic bone agent (only Sm-153-HEDP, Re-186 HEDP or Re-188-HEDP) within 3 months. Prior treatment with other radiotherapeutic bone agents (e.g., Sr-89-chloride, P-32 -phosphate) within 6 months. 7. Patients receiving bisphosphonate therapy must be discontinued for at least 2 weeks prior to treatment with Re-188-HEDP. 8. Receipt of any other investigational drug within 4 weeks of study entry. 9. Previous hemi-body external radiation therapy. 10. Receipt of external beam radiation for bone metastases with irradiation of bone marrow more than 25%, within 6 months of study entry. Related to the patient: 11. Known hypersensitivity to 5-FU, Re-188-HEDP, Capecitabine or any of the excipients, or phosphate compounds. 12. Patients whose medical history includes clinically significant bleeding disorders which might be exacerbated by study medication. 13. Known deficiency of dihydropyrimidine dehydrogenase (DPD). 14. Patients with concurrent illnesses or treatments that might preclude study completion or interfere with study results. 15. Patients with active CNS (grade 2 or higher) or epidural brain metastasis. 16. Clinical diagnosis of disseminated intravascular coagulation 17. Absolute neutrophil count, ANC 1.5 x ULN. 23. SGOT/AST > 2.5 x ULN or SGPT/ALT 2.5 x ULN.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim of the phase I part of this study is to establish the safety profile and to determine the maximum tolerated dose of capecitabine combined with Re-188-HEDP. The primary aim of the phase II part of this study is to obtain insight in the efficacy of Re-188-HEDP combined with capcitabine, as reflected by PSA. ;Secondary Objective: Secondary objectives of the study are to determine the biodistribution of Re-188-HEDP when combined with capecitabine; to study heamtological toxicity; to monitor pain and analgesic consumption; to monitor quality of life.;Primary end point(s): Cohorts of three successive patients will be treated with a combination of rhenium-188-HEDP and an increasing dose of Xeloda. If one or two DLT's occur in the cohort of three patients then the cohort will be increased to six patients. If maximum two out of six patients have a DLT then the next cohort will be tested. If at least three out of three patients or three out of six patients have a DLT then the MTD can be determined. | — |
Countries
Netherlands
Outcome results
None listed