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


Phase 2
18 Years
N/A
Open (Enrolling)
Male
Adenocarcinoma of the Prostate

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Trial Information

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


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


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate to Olaparib

Outcome 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

Outcome Time Frame:

Response will be evaluated 6 months post trial entry

Safety Issue:

No

Principal Investigator

Johann deBono

Investigator Role:

Principal Investigator

Investigator Affiliation:

Institute of Cancer Research, United Kingdom

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

ICR-CTSU/2011/10030

NCT ID:

NCT01682772

Start Date:

July 2012

Completion Date:

July 2015

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Olaparib
  • Adenocarcinoma
  • Prostate
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms

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