Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis

NCT03047135 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: J16163IRB00114635
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 4

Brief Summary

Olaparib has demonstrated preliminary efficacy in metastatic castration-resistant prostate cancer. In a trial of 49 evaluable patients treated with olaparib, 11 / 49 experienced a PSA response, and every patient with a radiographic response also had a PSA5 response. Ten of 11 responders had mutations in DNA repair genes. While PARP inhibition is showing promise in these initial studies, reserving its use for end-stage patients may not be the optimal timing for olaparib therapy in some patients. In addition, PARP enzymes function in roles beyond DNA repair, and specifically for prostate cancer are involved transcriptional regulation of the androgen receptor. PARP inhibition has not been tested in earlier disease states for prostate cancer.

Conditions

Prostate

Keywords

high-risk biochemically-recurrent

Outcome Measures

Primary Outcomes (1)

• PSA50 Response Rate to Olaparib for Patients With High-risk Biochemically-recurrent Prostate Cancer

  Number of participants with PSA50 response defined as at least a 50% decline in Prostate Specific Antigen (PSA) from baseline value, confirmed with a second measurement at least 4 weeks apart.

  6 years 2 months

Secondary Outcomes (4)

• Treatment-related Adverse Events as Assessed by CTCAE v4.0

  Baseline to End of Treatment

• PSA Progression-free Survival

  7 years

• PSA Doubling From Baseline

  7 years

• Duration of Undetectable PSA

  7 years

Study Arms (1)

Olaparib 300 mg BID

EXPERIMENTAL

Patients will be administered olaparib orally twice daily at 300mg bid continually. Two 150mg of olaparib tablets should be taken twice daily, approximately 12 hours apart with one glass of water.

Drug: Olaparib

Interventions

Olaparib DRUG

Olaparib will be dispensed to patients on Day 1 and every 28 days thereafter until the patient completes the study, withdraws from the study or closure of the study.

Olaparib 300 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of adenocarcinoma of the prostate
• Prior local therapy with prostatectomy required, with available tissue from prostatectomy specimen to send for genomic and transcriptomic testing.
• Prior salvage or adjuvant radiation therapy is allowed but not mandated. Radiation therapy must have been completed for at least 6 months.
• Absolute PSA ≥1 ng/ml. Prior undetectable PSA post-prostatectomy is not required.
• PSADT ≤6 months, based upon ≥3 consecutive measurements collected in the past 12 months, at least 4 weeks apart
• No radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 4 weeks.
• Serum testosterone ≥ 150 ng/dl
• Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 75 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) \<2.5 x institutional upper limit of normal. Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
• Patients must have creatinine clearance estimated using the Cockcroft
• Gault equation of ≥51 mL/min:

You may not qualify if:

• Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary; prior ADT for biochemical recurrence is allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (\>150 ng/dl). The total duration of prior ADT should not exceed 24 months.
• Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
• Prior treatment with intravenous chemotherapy.
• Involvement in the planning and/or conduct of the study
• Participation in another clinical study with an investigational product during the last 1 month.
• Any previous treatment with PARP inhibitor, including olaparib
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• 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 CYP3A inducers (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 phenobarbital and 3 weeks for other agents.
• Myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• 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, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Known hypersensitivity to olaparib or any of the excipients of the product.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AstraZeneca: collaborator

Study Sites (4)

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

Related Publications (1)

• Marshall CH, Teply BA, Lu J, Oliveira L, Wang H, Mao SS, Kelly WK, Paller CJ, Markowski MC, Denmeade SR, King S, Sullivan R, Davicioni E, Proudfoot JA, Eisenberger MA, Carducci MA, Lotan TL, Antonarakis ES. Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Oct 1;10(10):1400-1408. doi: 10.1001/jamaoncol.2024.3074.

  PMID: 39172479 DERIVED

MeSH Terms

Interventions

olaparib

Results Point of Contact

• Title: Catherine Handy Marshall, MD
• Organization: Johns Hopkins University

chm@jhmi.edu

410-955-0231

Study Officials

• Catherine H Marshall, MD

  Johns Hopkins University

  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: February 6, 2017
• First Posted: February 8, 2017
• Study Start: March 1, 2017
• Primary Completion: May 24, 2023
• Study Completion: May 1, 2026
• Last Updated: June 17, 2025
• Results First Posted: July 3, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)