The objective of the study (phase 2) is to evaluate the effectiveness of AMG 102 in combination with Mitoxantrone and Prednisone in previously treated subjects with castrate resistant prostate cancer.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 2;
To estimate with adequate precision the effect of the addition of AMG 102 to
MP, compared with placebo + MP, as assessed by the hazard ratio (HR) for
overall survival (OS) of previously treated subjects with castrate resistant
prostate cancer (CRPC).
Secondary outcome
Phase 2;
- Progression free survival (PFS), objective response rate (ORR) as measured by
modified RECIST, percentage changes in prostate specific antigen (PSA) level
and response rates.
- Patient reported outcomes, including pain.
- The incidence of adverse events, laboratory abnormalities.
- The incidence of anti-AMG 102 antibody formation.
- Pharmacokinetics (PK): Cmax and Cmin for AMG 102
Background summary
In this study, the experimental study drug AMG 102, in combination with
Mitoxantrone and Prednison, is evaluated for the treatment of patients with
previously treated Castrate Resistant Prostate Cancer. AMG 102 is a fully human
monoclonal antibody against hepatocyte growth factor that blocks binding of
HSF/SF to it's receptor c-Met, inhibiting HGF/c-Met-driven activities in cells.
The expression of c-Met has been linked to disease progression in prostate
cancer, so AMG 102 might delay the progression. AMG 102 is being tested in
combination with Mitoxantrone and Prednison (standard of care) to see if it
delays disease progression. AMG 102 is not approved by any regulatory
organisation.
Study objective
The objective of the study (phase 2) is to evaluate the effectiveness of AMG
102 in combination with Mitoxantrone and Prednisone in previously treated
subjects with castrate resistant prostate cancer.
Study design
This study has two parts; In Phase 2 the Dutch hospitals will participate.
Phase 2 is a randomized, double-blind portion of this study designed to
evaluate the efficacy, safety and PK of AMG 102 in combination with
Mitoxantrone and Prednisone (MP) in subjects with previously treated Castrate
Resistant Prostate Cancer. Phase 2 will commence upon identification of the
appropriate dose of AMG 102. Assuming the 15 mg/kg Q3W dose level is
determined, 135 subjects will be rendomized in a 1:1:1 ration to receive MP+15
mg/kg AMG 102 (arm A), MP+7.5 mg/kg (arm B) or MP+placebo (arm C), for a
maximum of 12 cycles. If the outcome of the Phase 1 study is that the
appropriate dose of AMG 102 is 7.5 mg/kg or 5 mg/kg , than 90 subjects will be
randomized in a 1:1 ratio receiving MP+7.5/5 mg/kg or MP+placebo.
There will be a 28 days screening period, a 12 cycle (Q3W) treatment period,
after the end of treatment a safety follow up in 30 days, a 60 day follow up
and a long term follow up of 36 months (Q3M) after the 30 day safety follow up.
Intervention
All Participating patients will receive AMG 102 Q3W in dose 15, 7.5, 5mg/kg or
placebo on day 1 of each cycle.
Study burden and risks
During the screening the following assessments will be done; - ECG, MUGA/ECHO,
blood samples, bone scan, CT/MRI, physical exam
During the treatment phase; the estimated treatment period will be 36 weeks.
the patient should visit the hospital every three weeks (12 times) for
medication dosing and laboratory assessments. Also some questinaires needs to
be filled out. In cycle 5, 9 and 12 radiological assessments will be done.
The risks of participation are small. Patients might receive AMG 102 and
therefore have a chance on a possible positive effect of AMG 102. The treatment
options for this patient population are small. If there are situations that are
not acceptable (for the patient or the investigator) the patient is always able
to stop with the study.
Minervum 7061
4800DH Breda
NL
Minervum 7061
4800DH Breda
NL
Listed location countries
Age
Inclusion criteria
* Pathologically confirmed adenocarcinoma of the prostate
* Radiographic evidence of metastatic disease
* Progressive disease meeting at least one of the following criteria:
1) a sequence of at least 2 rising PSA values measured at a minimum of 1
week apart with a 2 ng/mL minimum starting value, or
2) progression according to RECIST criteria for measurable lesions, or
3) appearance of 2 or more new lesions on bone scan.
* History of prior taxane-based chemotherapy for metastatic prostate cancer; no
more than one prior chemotherapy regimen for CRPC is allowed (estramustine
will be considered as chemotherapy)
* ECOG Performance status 0 or 1
* Life expectancy * 3 months
* Men * 18 years of age
Exclusion criteria
* Treatment with external beam radiotherapy * 14 days before enrollment or
radiopharmaceutical * 8 weeks
* * 4 weeks since receipt of most recent prior chemotherapy, non-GnRH analog hormonal therapy (except for continuing corticosteroids) or other systemic therapy to treat prostate cancer and <6 weeks since receipt of prior bevacizumab.
* Subjects with evidence of an antiandrogen withdrawal response must demonstrate objective or PSA progression following the response.
* Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area).
* Significant cardiovascular disease (CHF class III or IV, uncontrolled angina, MI within 6 months of enrollment); patients with medically stable atrial fibrillation may be included.
* LVEF < 50% by MUGA or ECHO
* Treatment of infection with systemic anti-infectives within 7 days before enrollment (with the exception of uncomplicated urinary tract infection)
* Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except that use of low dose coumarin-type anticoagulants or heparins for prophylaxis against central venous catheter thrombosis is allowed
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 |
|---|---|
| EudraCT | EUCTR2008-004355-30-NL |
| ClinicalTrials.gov | NCT-nummernognietbekend |
| CCMO | NL25740.029.08 |