Primary objective:To compare the clinical benifit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens, one of…
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Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is:
Overall survival
Secondary outcome
Secundary efficacy endpoints:
Proportion of patients achieving a PSA decline >= 50% according to the PSA
Working Group criteria
Time-to-PSA progression based on PSA WG criteria
Progression-free survival (PFS) based on imaging studies
Other endpoints:
Proportion of patients with objective tumor response by modified RECIST
(baseline lymph nodes size must be >= 2 cm to be considered a target lesion)
Proportion of patients experiencing pain palliation using BPI-SF and analgesic
score
Time to pain progression
Time to first skeletal-related event
Modified PFS based on criteria for discontinuation of study treatment
Proportion of patients achieving a decline in circulation tumor cells
(CTCs)/7.5 ml to less than 5
Quality of life total score and each subscale score as assessed by FACT-P
Safety endpoints:
All patients who receive at least one dose of abiraterone acetate or placebo
will be analyzed for safety. Safety summary will include adverse events,
clinical laboratories parameters, and vital signs. Serious adverse events and
deaths will be listed.
Background summary
Despite the improved survival in CRPC patients treated with docetaxel-based
regimens, the median survival of patients receiving docetaxel chemotherapy
17.5-18.9 months. Once the disease progresses after failing docetaxel-based
therapy, there is no treatment that hase proven to improve survival. Thus, new
therapies are urgently needed.
Recently, phase I and II studies have been carried out with Abiraterone Acetate
in patients with CRPC. Antitumor effects were evident with PSA response and
durable objective responses.
The mechanisms of actions of abiraterone acetate and docetaxel are not
overlapping. In a recently conducted Phase 2 study where abiraterone acetate
was administered to patients with advanced prostate cancer who had progressive
disease after docetaxel-based chemotherapy, approximately half of the patients
had a PSA reduction of > 50%. In patients with soft tissue metastatis on
imaging studies, tumor shrinkage was observed as well. Therefore, it appears
that resistance to docetaxel is independent of sensitivity to
androgen-deprivation therapy.
A Phase 2 study was conducted to evaluate the safety and efficacy of
abiraterone acetate in castration resistant prostate cancer (CRPC) after
failing docetaxel-based chemotherapy while receiving low dose prednisone.
Preliminary data so far shows few adverse events. In particular, adverse events
known to be associated with abiraterone acetate monotherapy, namely,
hypokalemia, hypertension, and fluid retention appear to be less frequent when
abiraterone acetate is used in combination with low-dose prednisone. In this
Phase 3 study, prednisone 5 mg bid has been selected for use in both study
treatment groups. The use of prednisone as a single agent, sometimes prescribed
ot palliate symptoms in advanced CRPC also justifies the placebo-controlled
design where the placebo group will receive low dose prednisone rather than no
treatment.
The primary hypthesis of this randomized, double-blind, placebo-controlled
study is that patients receiving abiraterone acetate and prednisone will
achieve a 25% improvement in overall survival compared with patients receiving
placebo and prednisone. It is also anticipated that abiraterone acetate will
increase the proportion of patients gaining PSA responses as defined by PSA WG
criteria, prolong the PSA and radiographic progression-free survival, possibly
palliate pain, reduce skeletal-related events due to metastatic bone disease
and improve QOL.
Study objective
Primary objective:
To compare the clinical benifit of abiraterone acetate plus prednisone with
placebo plus prednisone in patients with metastatic castration-resistant
prostate cancer (CRPC) who have failed one or two chemotherapy regimens, one of
which contains docataxel.
Secondary objectives:
To further evaluate the safety profile of abiraterone acetate plus prednisone
To further characterize the PK of abiraterone acetate when administered
concurrently with prednisone
To further explore the potential utility of CTC's as a surrogate for clinical
benefit
To evaluate the impact of abiraterone acetate plus prednisone on health related
quality of life (QOL)
Study design
Structure:
Phase 3 multinational, multicenter, randomized, double-blind,
placebo-controlled study with a randomization allocation of 2:1 (abiraterone
acetate : placebo). Abiraterone acetate and placebo tablets will be referred to
a study medication in a blinded fashion.
Randomization will be stratified according to the following:
ECOG performance status: 0-1 versus 2
Worst pain over the past 24 hours on BPI-SF: 0-3 (absent) versus 4-10 (present)
1 versus 2 prior chemotherapy regimens
Type of progression: PSA only versus radiographic progression
Intervention
Patients randomized to the abiraterone acetate group will receive a dose of
1000 mg daily (QD). Study medication will be administered as 4 x 250-mg
abiraterone acetate tablets or 4 placebo tablets.
Prednisone will be administered as 5 mg orally twice a day (bid) for both
groups.
Study burden and risks
Participating patients need to come to the site for regular visits: screening
visit, day 1 cycle 1, day 15 cycle 1, day 1 every following cycle and end of
study visit.
During these visits the following procedures will be performed: completion of
QoL-questionnaire, analgesic usage questionnaire, completion of fatigue scale,
physical examination, vital signs, ECG, MUGA-scan or cardiac echo, assessment
of adverse events, bloodsamples, urinalysis, CT-/MRI-scan, bone scan (see
protocol page 77).
In a recently conducted phase 2 study to evaluate the safety and efficacy of
abiraterone acetate in CRPC after failing docetaxel-based chemotherapy while
receiving low dose prednisone half of the patients had a PSA reduction of >=
50%. In patients with soft tissue metastasis tumor shrinkage was observed as
well. This study showed few adverse events.
Therefore from the risk benefit assessment it seems that treatment effect will
be greater than the risk for patients when participating in the study.
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10990 Wilshire Blvd., Suite 1200
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Age
Inclusion criteria
4. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
5. At least one but not more than 2 cytotoxic chemotherapy regimens for metastatic castration-resistant prostate cancer. At least one regimen must have contained docetaxel.
6. Documented prostate cancer progression by at least the following:
* PSA progression according to the PSA WG eligibility criteria (protocol appendix 3)
* Soft tissue disease progression by modified RECIST criteria (protocol appendix 4)
* Metastatic bone disease on bone scan with >= 2 new lesions and a concurrent PSA >= 5 ng/mL
7. Ongoing androgen deprivation with serum testosterone < 50 ng/dL
8. (ECOG) Performance Status of <= 2
9. Hemoglobin >= 9.0 g/dL independent of transfusion
10. Platelet count >= 100,000/µL
11. Serum albumin >= 3.0 g/dL
12. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance of 60 mL/min
13. Serum potassium >= 3.5 mmol/L
Exclusion criteria
1. Serious or uncontrolled co-existing non-malignant disease, including active and uncontrolled infection
2. Abnormal liver functions consisting of any of the following:
* Serum bilirubin >= 1.5 x ULN
* AST or ALT >= 2.5 x ULN (for patients with known liver metastatis, AST or ALT <= 5 x ULN is allowed)
3. Uncontrolled hypertension (systolic BP >= 160 mmHg, or diastolic BP >= 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.
4. Active or symptomatic viral hepatic or chronic liver disease
5. History of pituitary or adrenal dysfunction
6. Clinically significant heart disease
7. Other malignancy, except non-melanoma skin cancer, with a >= 30% probability of recurrence within 12 months.
8. Known brain metastatis
9. History of gastrointestinal disorders which may interfere with the absorption of the study drug.
11. Prior therapy with ketoconazole for prostate cancer
12. Surgery or local prostatic intervention within 30 days of first dose.
13. Radiotherapy, chemotherapy or immunotherapy within 30 days or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 day 1.
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 | EUCTR2007-005837-13-NL |
| CCMO | NL22011.091.08 |