Breast cancer with painful bone metastases. MedDRA version: 8.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Related to breast cancer: Histologically documented carcinoma of the breast, resistant to both taxanes and Anthracycline-containing chemotherapy regimen or resistant to taxanes and for whom further Anthracycline therapy is not indicated. Bone pain and/or pain medication is required for phase II testing. Presence of more than one osteoblastic bone metastasis confirmed by 99mTc-labeled bisphosphonates bone scan performed within 8 weeks prior to study entry. Presence of bidimensionally measurable disease as reflected by at least one measurable soft tissue lesion on CT-scan performed within 4 weeks prior to study entry. Karnofsky performance status >60% (Appendix: IV). Life expectancy of at least 3 months. Patients with lower urinary tract obstruction or incontinence must consent to catheterization of the bladder for up to 8 hours after administration of Re-188-HEDP. Related to the patient: Age >18 years. 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 breast 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 breast cancer (but not including basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix). Related to previous or concomitant therapies: 3. Previous chemotherapy within 4 weeks prior to screening. 4. Any other medicine taken with the intension to treat the disease. 5. Use of Interferon-alpha, Allopurinol, Sorivudine and analogues and Folinic acid. 6. Prior treatment with a systemic radiotherapeutic bone agent (only 153Sm-EDTMP, Re 186-HEDP or Re-188-HEDP) within 3 months. Prior treatment with other radiotherapeutic bone agents (e.g., 89Sr-chloride, 32P -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: 10. Known hypersensitivity to 5-FU, Re-188-HEDP, Capecitabine or any of the excipients, or phosphate compounds. 11. Patients whose medical history includes clinically significant bleeding disorders which might be exacerbated by study medication. 12. Known deficiency of dihydropyrimidine dehydrogenase (DPD). 13. Patients with concurrent illnesses or treatments that might preclude study completion or interfere with study results. 14. Patients with a history of dementia, seizures, central nervous system disorders, or psychiatric disability thought to be clinically significant in the opinion of the investigator and adversely affecting patient compliance with drug intake. 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. 22. SGOT/ASAT > 2.5 x ULN or SGPT/ALAT 2.5 x ULN.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the phase I study will be to investigate the maximum tolerated dose of Re-188-HEDP for the combined use with Capecitabine.The primary objective of the phase II part of the study will be to investigate the efficacy of Re-188-HEDP combined with Capecitabine, as determined by pain.;Secondary Objective: Secondary aims:- to determine the biodistribution of Re-188-HEDP when combined with Capecitabine- to study haematological toxicity- to monitor objective tumor response (RECIST)- to monitor analgesic consumption- to monitor HRQOL (Quality of life);Primary end point(s): Cohorts of three successive patients will be treated with a combination of Capecitabine and and increasing dose of Re-188-HEDP. If one or two DLT’s occur in the cohort of 3 patients then the cohort will be increased to 6 patients. If maximum 2 out of 6 patients have a DLT then the next cohort will be tested. If at least 3 out of 3 patients, or 3 out of 6 patients have a DLT then the MTD can be determined. | — |
Countries
Netherlands
Outcome results
None listed