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Adenocarcinoma of the ProstatePhase 2TOPARPNCT01682772

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

A Phase 2 study testing Olaparib in people with Adenocarcinoma of the Prostate, run by Institute of Cancer Research, United Kingdom at 2 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Adenocarcinoma of the Prostate
What is being tested?
Olaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
2 sitesUnited Kingdom
Study dates
Jul 2012to Feb 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject capable of understanding \& complying with protocol requirements \& signed the informed consent form
  • Minimum age 18 years
  • Histologically confirmed adenocarcinoma of the prostate with tumour tissue available for molecular analyses
  • 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
  • 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
  • Documented prostate cancer progression as described in the protocol.
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  • 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.
  • Eastern Cooperative Oncology Group Performance Status of 0, 1, 2
  • Life expectancy > 12 weeks
  • Able to swallow a whole tablet
  • 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
  • Agreeable to have all the biomarker studies including the paired fresh tumour biopsies.
  • 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.
  • Adequate bone marrow, hepatic \& renal function as defined in the protocol
  • For Part B only, patients must have genomic defects associated with olaparib sensitivity identified by NGS by the central lab.

Who cannot join

  • Surgery, or local prostatic intervention (excluding a prostatic biopsy) less than 28 days of Cycle 1 Day 1
  • 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
  • Prior treatment with a PARP inhibitor, platinum, cyclophosphamide or mitoxantrone chemotherapy
  • 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
  • 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
  • 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
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  • Patients with myelodysplastic syndrome/acute myeloid leukaemia
  • Patients with known symptomatic brain metastasis are not suitable for enrollment. Patients with asymptomatic, stable, treated brain metastases are eligible for study entry
  • Patients with symptomatic or impending cord compression unless appropriately treated beforehand \& clinically stable \& asymptomatic
  • 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
  • Patients receiving any of the following classes of inhibitors of CYP3A4 (see protocol for guidelines \& wash out periods)
  • Patients with gastrointestinal disorders likely to interfere with absorption of the study medication
  • 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
  • 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

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • University College Hospital London

    London, NW1 2BU

  • Royal Marsden NHS Foundation Trust

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

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

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.

Read the 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

Being tested
Olaparib
Keywords
Olaparib, Adenocarcinoma, Prostate
Medical subject headings
Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaparibDrug

    Also called AZD2281

    Until objective disease progression, unacceptable toxicity or patient withdrawal for whatever reason

Study groups in NCT01682772
Study groupRoleWhat they receive
Olaparib 400mgExperimentalOral Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle
Receives: Drug: Olaparib
Olaparib 300mgExperimentalOral Olaparib at a dose of 300mg twice daily, continuously on a 28 day cycle
Receives: Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response rate to Olaparib

    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

    Measured: Response will be evaluated 6 months post trial entry

Secondary outcomes (9)

  1. Radiographic progression free survival

    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

    Measured: Radiographic progression free survival will be evaluated 6 months post trial entry

  2. Progression free survival

    PFS will be measured from date of trial entry until radiographic progression, unequivocal clinical progression or death

    Measured: Progression free survival will be evaluated 6 months post trial entry

  3. Time to PSA Progression

    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.

    Measured: Time to PSA progression will be evaluated 6 months post trial entry

  4. CTC count conversion rate

    Proportion of patients with conversion of CTC count from ≥5/7.5ml blood at baseline to <5/7.5ml blood nadir

    Measured: CTC count conversion rate will be evaluated 6 months post trial entry

  5. Duration of PSA response

    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.

    Measured: Duration of PSA response will be evaluated 6 months post trial entry

  6. Number of participants with grade 3 or 4 adverse events as a measure of safety and tolerability.

    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

    Measured: 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.

  7. Time to radiographic progression

    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.

    Measured: Will be evaluated 6 months post trial entry

  8. Overall survival

    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

    Measured: Will be evaluated 6 months post trial entry

  9. PSA objective response

    PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2.

    Measured: Will be evaluated 6 months post trial entry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionMar 2019
  4. Study completionFeb 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01682772
Sponsor's protocol ID
ICR-CTSU/2011/10030
Other IDs
2011-000601-49, CRUK/C12540/A12354, ISRCTN15124653, ISS22810018
Acronym
TOPARP
Status last verified
Aug 2019
First submitted
27 Jul 2012
Last updated
15 Aug 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Carmichael J, Figueiredo I, Gurel B, Beije N, Yuan W, Rekowski J, Seed G, Carreira S, Bertan C, Fenor de La Maza MLD, Chandran K, Neeb A, Welti J, Gallagher L, Bogdan D, Crespo M, Riisnaes R, Ferreira A, Miranda S, Lu J, Shen MM, Hall E, Porta N, Westaby D, Guo C, Grochot R, Lord CJ, Mateo J, Sharp A, de Bono J. RNASEH2B loss and PARP inhibition in advanced prostate cancer. J Clin Invest. 2024 Jun 4;134(21):e178278. doi: 10.1172/JCI178278.

    PubMed 38833311

  • Mateo J, Porta N, Bianchini D, McGovern U, Elliott T, Jones R, Syndikus I, Ralph C, Jain S, Varughese M, Parikh O, Crabb S, Robinson A, McLaren D, Birtle A, Tanguay J, Miranda S, Figueiredo I, Seed G, Bertan C, Flohr P, Ebbs B, Rescigno P, Fowler G, Ferreira A, Riisnaes R, Pereira R, Curcean A, Chandler R, Clarke M, Gurel B, Crespo M, Nava Rodrigues D, Sandhu S, Espinasse A, Chatfield P, Tunariu N, Yuan W, Hall E, Carreira S, de Bono JS. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jan;21(1):162-174. doi: 10.1016/S1470-2045(19)30684-9. Epub 2019 Dec 2.

    PubMed 31806540

  • Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. doi: 10.1056/NEJMoa1506859.

    PubMed 26510020

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib in people with Adenocarcinoma of the Prostate, run by Institute of Cancer Research, United Kingdom at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate to Olaparib (time frame: Response will be evaluated 6 months post trial entry). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01682772, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2019.

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