A randomised phase II study of repeated Rhenium-188 HEDP combined with Docetaxel versus Docetaxel alone in castration resistant prostate cancer (CRPC) metastatic to bone*

Prostate cancer is the most common cancer in men in Western Europe and about 30
percent of these patients will develop metastatic disease. The skeleton is
involved in more than 80% of the patients with metastatic progression. These
bone metastases are associated with severe pain, pathologic fractures, bone
marrow insufficiency and spinal cord compression. First line treatment consists
of androgen suppression. Although initially the majority of patients is
responding to androgen deprivation, after an average of 18 months the cancer
will become hormone refractory leading to progressive disease and high
morbidity. The median survival in hormone refractory patients is about 12
months. Recent studies have shown not only a quality of life benefit but also
for the first time a survival benefit for men treated with Docetaxel. In
addition, patients are often treated with bone seeking radionuclides to
palliate bone pain. Recent studies suggest a survival benefit and better
quality of life for patients that are treated with the combination of Docetaxel
en radionuclidetherapy.

To compare the effect of standard care (Docetaxel monotherapy) versus the
combination of Docetaxel with Rhenium-188 HEDP for the treatment of patients
with progressive castration resistant prostate carcinoma metastatic tot bone.

This is a randomized phase II study comparing a schedule of repeated
administration of the bone-seeking radionuclide, Re-188 HEDP combined with
3-weekly Taxotere (Optimum dose schedule to be determined by ongoing Phase 1
study) with the standard schedule of Taxotere 3-weekly for a maximum of 10
cycles. The experimental arm will consist of 3 cycles of Taxotere 75mg/m2
followed by a treatment of Rhenium-188 HEDP (MTD), followed by 3 further cycles
of Taxotere 75mg/m2 followed by a second treatment of Rhenium-188 HEDP
followed by a maximum of 4 further cycles of Taxotere. Patients for inclusion
will have progressive prostate cancer and painful skeletal. Imaging (up to 8
weeks before treatment) and PSA measurement (3 assessments with at least 1 week
interval) will be done at baseline to assess disease status and the extent of
metastatic disease. The patients will be followed for 24 weeks after the last
treatment. Disease status, palliative response and safety will be assessed
during this study period.
Clinical outcome will be determined at 9, 12, 18 and 24 months after treatment,
as well as hematology and clinical chemistry to assess chronic toxicity, if
any. Survival data will be collected at 12, 18 and 24 months after the first
treatment.

Randomisation between:
- Docetaxel 75 mg/m2 3-weekly for a maximum of 10 cycles

and

- 3 cycles Docetaxel 75 mg/m2, followed by a gift Rhenium-188 HEDP, followed by
3 cycles Docetaxel 75 mg/m2, followed by a gift Rhenium-188 HEDP, followed by a
maximum of 4 cyclesDocetaxel 75 mg/m2

Burden
- Patients in arm B will have two extra visits to the hospital (hospital stay
0.5 day)
- Additional bloodsamples: after the two cycles of rhenium (2x), during
follow-up (4x) and in case the patient participates in a side study (optional):
3 times 9 ml. For the last no additional venapunctares are necessary, but blood
will be drawn during a regular punction
- Patients will be asked to fill in questionnaires about quality of life

Risks
- The most important risk is hematological toxicity, especially leucopenia and
trombocytopenia. However, the phase I trial has showed that the combination of
Rhenium and Docetaxel is generally well tolerated and hematological toxicity is
self limiting.