Clinical Trials /

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

NCT01682772

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TOPARP: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer
  • Official Title: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)

Clinical Trial IDs

  • ORG STUDY ID: ICR-CTSU/2011/10030
  • SECONDARY ID: 2011-000601-49
  • SECONDARY ID: CRUK/C12540/A12354
  • SECONDARY ID: ISRCTN15124653
  • SECONDARY ID: ISS22810018
  • NCT ID: NCT01682772

Conditions

  • Adenocarcinoma of the Prostate

Interventions

DrugSynonymsArms
OlaparibAZD2281Olaparib 300mg

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib 400mgExperimentalOral Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle
  • Olaparib
Olaparib 300mgExperimentalOral Olaparib at a dose of 300mg twice daily, continuously on a 28 day cycle
  • Olaparib

Eligibility 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. Note: For Part B, CTC count >5
             cells/7.5mls blood is not mandatory if patient has measurable disease by modified
             RECIST and a lesion >2cm and PSA greater than or equal to 2ng/ml at screening.

         14. Adequate bone marrow, hepatic & renal function as defined in the protocol

         15. For Part B only, patients must have genomic defects associated with olaparib
             sensitivity identified by NGS by the central lab.

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate to Olaparib
Time Frame:Response will be evaluated 6 months post trial entry
Safety Issue:
Description: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

Measure:Radiographic progression free survival
Time Frame:Radiographic progression free survival will be evaluated 6 months post trial entry
Safety Issue:
Description: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
Measure:Progression free survival
Time Frame:Progression free survival will be evaluated 6 months post trial entry
Safety Issue:
Description:PFS will be measured from date of trial entry until radiographic progression, unequivocal clinical progression or death
Measure:Time to PSA Progression
Time Frame:Time to PSA progression will be evaluated 6 months post trial entry
Safety Issue:
Description: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.
Measure:CTC count conversion rate
Time Frame:CTC count conversion rate will be evaluated 6 months post trial entry
Safety Issue:
Description:Proportion of patients with conversion of CTC count from ≥5/7.5ml blood at baseline to <5/7.5ml blood nadir
Measure:Duration of PSA response
Time Frame:Duration of PSA response will be evaluated 6 months post trial entry
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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
Measure:Time to radiographic progression
Time Frame:Will be evaluated 6 months post trial entry
Safety Issue:
Description: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.
Measure:Overall survival
Time Frame:Will be evaluated 6 months post trial entry
Safety Issue:
Description: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
Measure:PSA objective response
Time Frame:Will be evaluated 6 months post trial entry
Safety Issue:
Description:PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Institute of Cancer Research, United Kingdom

Trial Keywords

  • Olaparib
  • Adenocarcinoma
  • Prostate

Last Updated

August 13, 2019