TOPARP: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)
Recruitment status was: Recruiting
This is an open-label, single arm, two part adaptive design phase II trial of Olaparib in patients with advanced castration resistant prostate cancer.
The trial aims to evaluate the the anti-tumour activity of Olaparib in metastatic castration resistant prostate cancer, identify molecular signatures of tumour cells in responding and non-responding patients, and to identify predictive biomarkers of Olaparib response.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)|
- Response rate to Olaparib [ Time Frame: Response will be evaluated 6 months post trial entry ]
Response will be defined on the basis of the following outcomes, if any of these occur patients will be considered to have responded:
- Objective response by modified RECIST
- PSA decline of ≥50% according to the Prostate Cancer Working Group 2
- Conversion of circulating tumour cell count from ≥5 cells/7.5ml blood at baseline to <5 cells/7.5ml blood confirmed by at least two readings 4 weeks apart
- Radiographic progression free survival [ Time Frame: Radiographic progression free survival will be evaluated 6 months post trial entry ]rPFS will be defined by either RECIST progression and/or progression on bone scan. It will be measured from the date of trial entry to the first occurence of radiographic progression or death from any cause
- Progression free survival [ Time Frame: Progression free survival will be evaluated 6 months post trial entry ]PFS will be measured from date of trial entry until radiographic progression, unequivocal clinical progression or death
- Time to PSA Progression [ Time Frame: Time to PSA progression will be evaluated 6 months post trial entry ]For patients who have achieved ≥50% decrease from the cycle 1 day 1 (baseline), the PSA progression date is defined as the date that a ≥25% increase and an absolute increase of ≥2ng.mL above the nadir is documented. This must be confirmed by a second consecutive value. For patients without a PSA decrease of this magnitude or no decrease at all, PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline is documented. This must also be confirmed by a second consecutive value.
- CTC count conversion rate [ Time Frame: CTC count conversion rate will be evaluated 6 months post trial entry ]Proportion of patients with conversion of CTC count from ≥5/7.5ml blood at baseline to <5/7.5ml blood nadir
- Duration of PSA response [ Time Frame: Duration of PSA response will be evaluated 6 months post trial entry ]Duration of PSA response is calculated from the time the PSA value first declines by at least 50% of the cycle 1 day 1 (baseline) value (must be confirmed by a second value) until the time there is an increase of 25% of PSA nadir, provided the absolute increase is at least 2 ng/mL. The increase must be confirmed by a second consecutive measurement.
- Number of participants with grade 3 or 4 adverse events as a measure of safety and tolerability. [ Time Frame: Will be evaluated 1) when the first 5 and 10 participants have completed the 1st cycle of treatment and, 2) at 6 months post trial entry. ]The proportion of patients with grade 3/4 adverse events will be described along with other descriptive measures of safety and tolerability and evaluated by the IDMC
- Time to radiographic progression [ Time Frame: Will be evaluated 6 months post trial entry ]Time to radiographic progression (progression defined by either RECIST progression and /or progression on bone scan) will be measured from the date of trial entry to the first occurrence of radiographic progression. Death from prostate cancer or any other cause without prior radiographic evidence of progression will not count as an event.
- Overall survival [ Time Frame: Will be evaluated 6 months post trial entry ]OS will be measured from the date of trial entry to the date of death (whatever the cause). Survival time of living patients will be censored on the last date a patient is known to be alive or lost to follow-up
- PSA objective response [ Time Frame: Will be evaluated 6 months post trial entry ]PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Oral Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle
Until objective disease progression, unacceptable toxicity or patient withdrawal for whatever reason
Other Name: AZD2281
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682772
|Contact: TOPARP Trial Manager||020 8722 firstname.lastname@example.org|
|Royal Marsden NHS Foundation Trust||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|University College Hospital London||Not yet recruiting|
|London, United Kingdom, NW1 2BU|
|Principal Investigator:||Johann deBono||Institute of Cancer Research, United Kingdom|