Primary objectives:To establish a safe and effective dosing schedule for repeated administration of Rhenium-188 HEDP combined with Cabazitaxel in order to proceed with a Randomised Phase 2 trial designed to determine the clinical value of Rhenium-…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objectives:
To establish a safe and effective dosing schedule for repeated administration
of Rhenium-188 HEDP combined with Cabazitaxel in order to proceed with a
Randomised Phase 2 trial designed to determine the clinical value of
Rhenium-188 HEDP/Cabazitaxel using progression free survival as the primary
endpoint.
Phase I:
The Dose Limiting Toxicity (DLT) period is defined as 7 weeks from
administration of Rhenium. In no DLT occurs in this period, patients can be
included in the next dose level. If a DLT occurs in 1 of the 3 patients in a
particular treatment level, the group will be expanded to 6 patients. If 2 or
more of the group experience a DLT, we will treat the next 3 patients at the
previous dose level (i.e. If DLT in >2/6 at dose level 2, 3 patients will be
treated at dose level 1). If none of the group of 3 or <1/6 experience DLT, 3
patients will be treated at the next dose level. The final group of 3 patients
will be treated at a planned dose of 6 cycles of cabazitaxel 25mg/m2 and 2
cycles of Rhenium-188 HEDP (40 MBq/kg).
DLT is defined as:
- Hematological:
- Neutropenia: Grade 4 > 7days. Grade 3 when failure of count recovery to allow
for next cycle on time.
- Thrombopenia: All grade 4. Grade 3 when failure of count recovery to allow
for next cycle on time.
- Anemia: All grade 4.
-Non-hematological:
- All grade 4
- All grade 3 except for nausea, vomiting or diarrhea unless not recovered to
allow for next cycle on time.
N.B. Patients with grade 4 neutropenia >7 days during the first or second cycle
cabazitaxel will be excluded from the phase I study
Phase II:
Progression Free Survival (PFS) will be the primary efficacy endpoint.
Secondary endpoints are: PSA response, overall survival, pain response, and
quality of life
Secondary outcome
Secondary objectives:
Evaluate overall survival, PSA response, clinical benefit response (pain and
Quality of life), toxicity, RNA-expression profiles on trombocytes
Background summary
Prostate cancer is very common and often leads to bone metastases. Although
initially most patients respond to androgen deprivation, after approximately 18
months the cancer will become hormone refractory leading to progressive
disease. Since 2004 Docetaxel became standard chemotherapy for men with
metastatic CRPC leading to survival benefit. Several trials have shown
evidence of the disease modifying potential of bone seeking radionuclides.
Recent studies have shown an improvement of survival and quality of life when
Rhenium-186 HEDP was given in high dosage or repeatedly. Recently results of
our dosefinding trial (XRP6976J/6213) showed that combined therapy with
Docetaxel and Rhenium-186 HEDP is generally well tolerated in patients with
metastatic bone disease from prostate cancer. A phase II study (DOCET_L_04935)
will be conducted using 3 cycles of Docetaxel 75mg/m2 followed by Rhenium-188
HEDP 2500MBq, followed by another 3 cycles of Docetaxel, followed by
Rhenium-188 HEDP 1250MBq.
Cabazitaxel is a promising new drug to be used for the treatment of castrate
resistant prostate cancer (CRPC) after progression on Docetaxel therapy.
In this study, we build upon previous results and we aim to test wheather the
combination of Cabazitaxel with repeated Rhenium-188 HEDP is feasible and leads
to better PFS, OS and pain control compared to Cabazitaxel alone in patients
with mCRPC after progression of disease after first line docetaxel. We start
with a phase I dosefinding trial, immediately followed by a phase II trial if
the envisaged schedule is feasible.
Study objective
Primary objectives:
To establish a safe and effective dosing schedule for repeated administration
of Rhenium-188 HEDP combined with Cabazitaxel in order to proceed with a
Randomised Phase 2 trial designed to determine the clinical value of
Rhenium-188 HEDP/Cabazitaxel using progression free survival as the primary
endpoint.
Secondary objectives:
Evaluate overall survival, PSA response, clinical benefit response, toxicity
and RNA-expression profiles on trombocytes. Second side study will investigate
the influence of lipegfilgrastim on the incidence of neutropenic fever.
Study design
Trial design phase I (see appendix)
Trial design phase II:
Arm A: Cabazitaxel (20 or 25mg/m2) d1, q3 for a maximum of 10 cycles
Arm B: Cabazitaxel (20 or 25mg/m2) d1, q3 for a maximum of 10 cycles +
Rhenium-188 HEDP (dose schedule phase I)
All patients will receive 10 mg prednisone daily during Cabazitaxel treatment.
In phase II, an extra randomasation (1:1) will be performed; arm A will not
receive lipegfilgrastim after the first cycle of cabazitaxel, patients in arm B
will receive 1 injection of lipegfilgrastim after the first dose of
cabazitaxel.
Intervention
Randomization:
Phase II
Arm A: Cabazitaxel (20 or 25mg/m2) d1, q3 for a maximum of 10 cycles
Arm B: Cabazitaxel (20 or 25mg/m2) d1, q3 for a maximum of 10 cycles +
Rhenium-188 HEDP (dose schedule phase I)
All patients will receive 10 mg prednisone daily during Cabazitaxel treatment.
Side study; randomastion for lipegfilgrastim (1:1)
Study burden and risks
Burden:
- Blood tests will be done every weeks instead of 3-weekly during the phase I
part only. In the phase II part of the trial bloodtest will be performed before
every cycle according to standard care.
- Patients in arm B will have two extra visits to the hospital (hospital stay
0.5 days)
- 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 venapunctures are necessary, but blood
will be drawn during a regular punction.
- Patients will be asked to fill in questionairies about quality of life
Risks:
The most important risk is hematological toxicity, especially leucopenia and
thrombocytopenia. However, our phase I study combining rhenium and docetaxel
showed that combining of rhenium and Docetaxel is generally well tolerated and
hematological toxicity is self limiting. Therefore we suspect that the
combination of cabazitaxel with Rhenium will also be feasible.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Castration resistant prostate cancer with bone metastases
Exclusion criteria
patients with predominant visceral metastases. Bone marrow insuffiency
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 10793 |
| EudraCT | EUCTR2011-005116-28-NL |
| CCMO | NL38495.100.12 |