The Prostate CARE Study: Capecitabine (Xeloda??) combined with Rhenium-188-HEDP in hormone refractory prostate cancer patients with bone metastases; a Capecitabine phase I dose escalation study and phase II efficacy study.

Prostate cancer is currently one of the most common malignancies worldwide.
About 50-70% of patients with prostate cancer present a locally advanced stage
and about 15-30% have bone metastases at the time of diagnosis. Metastatic
disease may also develop after treatment for localized disease. Although a vast
majority of patients initially respond to hormone treatment most, if not all,
patients subsequently relapse and progresses from an androgen-dependent to an
androgen-independent state. Approximately 65% of patients with bone metastases
suffer from bone painand require palliative treatment.
Rhenium-188-HEDP is a radiopharmaceutical that has an affinity for skeletal
tissue and that concentrates in areas of bone turnover secondary to invasion by
tumor. It is used for the treatment of metastatic bone pain.
Capecitabine inhibits tumor growth and has a proven efficacy in patients with
colorectal and 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 prostate cancer patients, without
unacceptable hematotoxicity. This combined treatment may lead to improved pain
palliation and thus to a better quality of life.

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 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.

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

In phase I, after a screening procedure, three cohorts of 3 succesive patients
will be treated with 3 dosage levels of capecitabine and a fixed dose of
Re-188-HEDP (37MBq/kg). If a dose limiting toxicity occurs the cohort will be
increased to 6 patients. If at least 3 patients out of 6 (in one cohort) have a
dose limiting toxicity, the maximum tolerated dose can be determined (i.e. the
previous dosage level).
In phase II, after a screening procedure, all patients will undergo combined
treatment with the MTD of capecitabine combined with a fixed dose of
Re-188-HEDP.
In both phases the patient will undergo 1 total body scintigraphy 6 hours after
administration of re-188-HEDP, and urine collection during 8 hours.
Bloodsamples for safety will be taken each week. A bloodsample for PSA
measurement will be taken in weeks 1, 5 and 9. Patients will be asked to keep a
pain an medication diary throughout the study, and to fill out a HRQOL
questionnaire before treatment and in weeks 5 and 9.

The extra burden to the patient consists of:
1 screening visit
1 hospital admission for treatment with Re-188-HEDP
1 total body scan
2 outpatient visits
10 bloodsampling for safety and/or PSA
3 urine samples for saftey
keeping a pain and medication diary during 8 weeks
3 HRQOL questionnaires
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.