The Breast CARE Study: Capecitabine (Xeloda) combined with Rhenium-188-HEDP in breast cancer patients with bone metastases; a Re-188-HEDP phase I dose escalation study and phase II efficacy study.

Approximately 65% of patients with bone metastases suffer from bone pain.
Two-thirds of patients with breast cancer will develop metastatic bone disease.
The therapeutic options are rarely (if ever) curative, and at some point in
time the vast majority of patients suffering from osseous metastases will
develop progressive disease. Patients with progressive disease require
palliation for painful bone metastases.
Rhenium-188-HEDP is a new and attractive radiopharmaceutical for the treatment
of metastatic bone pain. It has an affinity for skeletal tissue and
concentrates in areas of bone turnover secondary to invasion by tumor.
Capecitabine inhibits tumor growth and has proven efficacy in patients with
breast cancer.
As capecitabine has proven radiosensitizing properties in other tumors, it
might be a potential radiosensitizer for the combined use with Re-188-HEDP in
breast cancer patients, without unacceptable hematotoxicity. Besides
improvement in cytostatic effect, this combined treatment could also lead to
improved pain palliation.

Phase I
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 Re-188-HEDP combined
with Capecitabine.
Phase II
The primary aim of the phase II part of this study is to obtain insight in the
efficacy of Re-188-HEDP combined with Capecitabine, as reflected by pain
response.

Secondary objectives of both studies will be:
To determine the biodistribution of Re-188-HEDP when combined with Capecitabine.
To study hematological toxicity.
To monitor objective tumour response, by means of RECIST criteria.
To monitor analgesic consumption.
To monitor quality of life by a HRQOL questionnaire.

This will be a combined phase I/II, uncontrolled, non randomized, open-label
study in breast cancer patients with osteoblastic bone metastasis.

Phase I:Cohorts of 3 successive patients will be treated with 3 dosage levels
of Re-188-HEDP in combination with a fixed dose of Capecitabine. If a dose
limiting toxicity occurs the cohort will be increased to 6 patients. If at
least 3 patients out of 6 have a dose limiting toxicity, the maximum tolerated
dose is reached.
Phase II:All patients will undergo combined treatment with the maximum
tolerated dose of Re-188-HEDP combined with a fixed dose of Capecitabine.
After administration of Re-199-HEDP the patient will undergo 1 total body
scintigraphy and urine collection during 8 hours. Bloodsamples for safety will
be taken every week. The CT scan (for inclusion) and after 3 cycles of
capecitabine are part of the normal routine patient care.

The extra burden to the patiënt consists of:
1 screening visit
1 hospital admission for treatment with Re-188-HEDP (12 hours)
1 total body scan
2 outpatient visits
10 bloodsampling for safety
3 urine samples for safety
The possible risks are related to the side effects of both capecitabine and
Re-188-HEDP, and the possibility of bruising from bloodsampling or intravenous
injection.
The radiation dose from Re-188-HEDP (mean dose 1400 mSv) does not form a large
risk to the patient and does not impose any restrictions for medical
investigations or treatments with radiation the patient may need in the future.

The patient may benefit from pain relief.