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

Institute of Cancer Research, United Kingdom

Status and phase

Unknown

Phase 2

Conditions

Adenocarcinoma of the Prostate

Treatments

Drug: Olaparib

Study type

Interventional

Funder types

Other

Identifiers

NCT01682772

2011-000601-49 (EudraCT Number)

CRUK/C12540/A12354 (Other Grant/Funding Number)

ISRCTN15124653 (Registry Identifier)

ISS22810018 (Other Grant/Funding Number)

ICR-CTSU/2011/10030

Details and patient eligibility

About

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.

Full 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

Enrollment

148 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
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.

Exclusion criteria

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
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