BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes

NCT03432897 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: BrUOG 337
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate approximately 3 months of treatment with the drug olaparib in patients with prostate cancer. A capsule formulation of olaparib (tradename Lynparza™) is approved by the United States Food and Drug Administration (FDA) for the treatment of women with advanced BRCA-mutated ovarian cancer. Olaparib is an investigational drug in prostate cancer. A tablet formulation of olaparib is being tested in this study. It is a new formulation which is more convenient for patients than the approved capsule formulation because fewer tablets of olaparib need to be taken daily than with capsules. The purpose of the study is to evaluate whether olaparib can reduce prostate cancer with defects in DNA repair genes when olaparib is given for approximately 3 months before surgery.

Conditions

Prostate Cancer; Adenocarcinoma of the Prostate

Keywords

High risk; Defects; prostate

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Prostate Specific Antigen (PSA) Response

  Response:Reduction of at least 50% in the prostate-specific antigen level from baseline Progression:A 25% increase in PSA from baseline Baseline then approximately 8 weeks later and 2 weeks post Olaparib, approximately 10-14 weeks after baseline and then approximately every 6 months for 2 years in follow-up.

  Throughout the trial for approximately 2 years

Secondary Outcomes (2)

• PSA Progression-free Survival of Olaparib and Radical Prostatectomy for Patients With Locally Advanced Prostate Cancer and Defects in DNA Repair Genes.

  Post treatment (approximately 8-12 weeks) and approximately every 6 months for 2 years.

• Safety of Olaparib Prior to Radical Prostatectomy for Patients With Locally Advanced Prostate Cancer

  Eight to 12 weeks prior to radical prostatectomy utilizing the descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for grading all adverse events.

Study Arms (1)

Treatment

EXPERIMENTAL

Olaparib 300 mg BID q 4 weeks for up to 3 cycles. The 3rd cycle will not be given if patient is found to progress post cycle 2. Between 22-42 days post Olaparib, patients will undergo a prostatectomy.

Drug: Olaparib Pill; Procedure: Prostatectomy

Interventions

Olaparib Pill DRUG

300 mg BID

Treatment

Prostatectomy PROCEDURE

22-42 days post Olaparib patients will undergo surgery

Treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study is for prostate cancer, therefore male participants only, are allowed.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy confirmed adenocarcinoma of the prostate.
• High risk for recurrence after prostatectomy including any of the following
• Lymph node involvement by radiographic criteria
• T3 or T4 disease by radiographic criteria
• T2 disease and either PSA \> 20 or Gleason 8,9 or 10
• Defects in any of the following genes:BRCA1, BRCA 2, ATM, CHEK1, CHEK2, FANCONIS ANEMIA (FANCL), HDAC2, PALB2, BARD1, BRIP1, CDK12, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L as assessed by Foundation Medicine FoundationOne assay on tumor tissue or cell-free DNA from peripheral blood via the FoundationACT assay.
• No distant visceral metastases.
• No prior chemotherapy or radiation for prostate cancer or PARP inhibitor. Prior and current hormone therapy (\< 6 months from start date on study) for prostate cancer is allowed. Patients are allowed to remain on hormone therapy on study.
• ECOG performance status 0-1.
• Age\>18.
• Required entry laboratory parameters
• ANC≥ 1,500 cells/mm3;
• Hemoglobin \> 10.0g/dL with no blood transfusion in the last 14 days
• Platelet count ≥100 x 109/L,
• Total bilirubin ≤ 1.5 x ULN,

You may not qualify if:

• Participation in another clinical study with an investigational anticancer product during the last 2 months (from day 1 of treatment on this trial). This pertains to treatment no trials the patient may only be seen in follow-up.
• Any previous treatment with PARP inhibitor for this or another cancer, including olaparib.
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors including lymphomas (without bone marrow involvement) which was curatively treated with no evidence of disease for ≥5 years. Diagnosis date and treatment confirmation required to be sent to BrUOG. Certification from treating physician that patient is disease free is required.
• Resting ECG with QTc \> 470 msec on 2 time-points within a 24 hour period or known family history of long QT syndrome
• Patients receiving any systemic chemotherapy or radiotherapy within 3 weeks prior to study treatment
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Concomitant use of the substrates of CYP3A4, CYP1A2, 2B6, 2C9, 2C19 and P-gp should be cautioned while on study.
• CYP3A4 - hormonal contraceptive, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus and quetiapine CYP1A2 - duloxetine, melatonin CYP2B6 - bupropion, efavirenz CYP2C9 - warfarin CYP2C19 - lansoprazole, omeprazole, S-mephenytoin P-gp - simvastatin, pravastatin, digoxin, dabigatran, colchicine OATP1B1 - bosentan, glibenclamide, repaglinide, statins and valsartan OCT1, MATE1, MATE2K - metformin OCT2 - serum creatinine OAT3 -furosemide, methotrexate
• Persistent toxicities deemed related to previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patients with brain metastases.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any prior major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.

Sponsors & Collaborators

• Brown University: lead
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Lifespan Cancer Institute: The Miriam and Rhode Island Hospitals

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

• Nientiedt C, Duensing A, Zschabitz S, Jager D, Hohenfellner M, Stenzinger A, Duensing S. PARP inhibition in prostate cancer. Genes Chromosomes Cancer. 2021 May;60(5):344-351. doi: 10.1002/gcc.22903. Epub 2020 Oct 28.

  PMID: 33084183 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; Prostatectomy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: BrUOG
• Organization: Brown Oncology Research Group

BrUOG@Brown.edu

4018633000

Study Officials

• Anthony Mega, MD

  BrUOG

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: February 14, 2018
• Study Start: May 25, 2018
• Primary Completion: December 15, 2020
• Study Completion: December 7, 2021
• Last Updated: July 8, 2025
• Results First Posted: February 3, 2022

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)