TOPARP: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Institute of Cancer Research, United Kingdom
Sponsor:
Collaborator:
Royal Marsden NHS Foundation Trust
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier:
NCT01682772
First received: July 27, 2012
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Drug: Olaparib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)

Resource links provided by NLM:


Further study details as provided by Institute of Cancer Research, United Kingdom:

Primary Outcome Measures:
  • Response rate to Olaparib [ Time Frame: Response will be evaluated 6 months post trial entry ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Radiographic progression free survival [ Time Frame: Radiographic progression free survival will be evaluated 6 months post trial entry ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2.


Estimated Enrollment: 89
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib
Oral Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle
Drug: Olaparib
Until objective disease progression, unacceptable toxicity or patient withdrawal for whatever reason
Other Name: AZD2281

Detailed Description:

Patients with advanced castration resistant prostate cancer will receive single agent Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle. Olaparib will be administered until objective disease progression or unacceptable toxicity or patient withdrawal for whatever reason

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject capable of understanding & complying with protocol requirements & signed the informed consent form
  2. Minimum age 18 years
  3. Histologically confirmed adenocarcinoma of the prostate with tumour tissue available for molecular analyses
  4. At least one but no more than two previous taxane-based chemotherapy regimens. If docetaxel chemotherapy is used more than once, this will be considered as one regime. Patients may have had prior exposure to cabazitaxel treatment
  5. At least 28 days since the completion of prior therapy, including major surgery, chemotherapy & other investigational agents. Clinically relevant sequelae should have resolved to grade 1 or less prior to recommencing treatment. For hormonal treatment & radiotherapy refer to the protocol guidelines
  6. Documented prostate cancer progression as described in the protocol.
  7. Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is being treated with LHRH agonists this must have been initiated at least 4 weeks prior to Cycle 1 Day 1 & must be continued throughout the study.
  8. Eastern Cooperative Oncology Group Performance Status of 0, 1, 2
  9. Life expectancy > 12 weeks
  10. Able to swallow a whole tablet
  11. Patient & the patient's partner of childbearing potential, must agree to use medically accepted methods of contraception during the course of the study & for 3 months after the last dose of study drug
  12. Agreeable to have all the biomarker studies including the paired fresh tumour biopsies.
  13. CTC count of 5 cells/7.5mls blood or more at screening
  14. Adequate bone marrow, hepatic & renal function as defined in the protocol

Exclusion Criteria:

  1. Surgery, or local prostatic intervention (excluding a prostatic biopsy) less than 28 days of Cycle 1 Day 1
  2. Less than 28 days from any active anticancer therapy or investigational agents. For hormonal treatment & radiotherapy refer to the guidelines outlined in the inclusion criteria
  3. Prior treatment with a PARP inhibitor, platinum, cyclophosphamide or mitoxantrone chemotherapy
  4. Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
  5. Any acute toxicities due to prior chemotherapy & / or radiotherapy that have not resolved to a NCI-CTCAE v4.02 grade 0 or 1 with the exception of chemotherapy induced alopecia & grade 2 peripheral neuropathy
  6. Malignancy within the previous 2-years with a > 30% probability of recurrence within 12 months with the exception of non-melanoma skin cancer, in-situ or superficial bladder cancer
  7. Patients with myelodysplastic syndrome/acute myeloid leukaemia
  8. Patients with known symptomatic brain metastasis are not suitable for enrollment. Patients with asymptomatic, stable, treated brain metastases are eligible for study entry
  9. Patients with symptomatic or impending cord compression unless appropriately treated beforehand & clinically stable & asymptomatic
  10. Patients who have experienced a seizure or seizures within 6 months of study treatment or who are currently being treated with cytochrome P450 enzyme inducing anti-epileptic drugs for seizures
  11. Patients receiving any of the following classes of inhibitors of CYP3A4 (see protocol for guidelines & wash out periods)
  12. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication
  13. Initiating bisphosphonate therapy or adjusting bisphosphonate dose/regimen within 30 days prior to Cycle 1 Day 1. Patients on a stable bisphosphonate regimen are eligible & may continue
  14. Presence of a condition or situation, which, may put the patient at significant risk, confound the study results, or interfere significantly with participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682772

Contacts
Contact: TOPARP Trial Manager 020 8722 4156 toparp-icrctsu@icr.ac.uk

Locations
United Kingdom
Royal Marsden NHS Foundation Trust Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
University College Hospital London Not yet recruiting
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Royal Marsden NHS Foundation Trust
Investigators
Principal Investigator: Johann deBono Institute of Cancer Research, United Kingdom
  More Information

No publications provided

Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT01682772     History of Changes
Other Study ID Numbers: ICR-CTSU/2011/10030, 2011-000601-49, CRUK/C12540/A12354, ISRCTN15124653, ISS22810018
Study First Received: July 27, 2012
Last Updated: September 10, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Institute of Cancer Research, United Kingdom:
Olaparib
Adenocarcinoma
Prostate

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 28, 2014