Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

NCT03570476 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: 9985NCI-2018-00977P30CA015704RG1718008
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well olaparib works in treating participants with prostate cancer that has not spread to other parts of the body (localized). Olaparib may stop the growth of tumor cells by interfering with the activity of a substance called PARP, which is inside cells. Giving olaparib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Prostate Adenocarcinoma Without Neuroendocrine Differentiation; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Pathologic Complete Response (pCR) Rate

  Percent of patients who achieve a pCR at the time of prostatectomy, after 12 weeks of neoadjuvant therapy with olaparib. PCR is defined as the absence of morphologically identifiable carcinoma in the prostatectomy specimen. Assessment will be based on the recommendations of the International Society of Urological Pathology (ISUP).

  At time of prostatectomy (at 12 weeks)

• Number of Participants With Adverse Events

  Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).

  Up to 30 days after the last dose of olaparib

Secondary Outcomes (2)

• Rate of Positive Surgical Margins

  At time of prostatectomy (at 12 weeks)

• Stage of Disease

  At time of prostatectomy (at 12 weeks)

Study Arms (1)

Treatment (olaparib, radical prostatectomy)

EXPERIMENTAL

Participants receive olaparib orally twice daily for 90 days in the absence of unacceptable toxicity. Beginning 1 day after last olaparib dose, participants undergo radical prostatectomy.

Drug: Olaparib; Procedure: Radical Prostatectomy

Interventions

Olaparib DRUG

Given orally

Also known as: AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (olaparib, radical prostatectomy)

Radical Prostatectomy PROCEDURE

Undergo surgery

Also known as: Prostatovesiculectomy

Treatment (olaparib, radical prostatectomy)

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Histologically confirmed adenocarcinoma of the prostate without morphologic neuroendocrine differentiation or small cell features.
• The presence of homologous recombination deficiency defined by either; A) Inherited pathogenic variant of BRCA2, ATM, BRCA1, PALB2 by a Clinical Laboratory Improvement Act (CLIA) level germline assay or B) have evidence by somatic sequencing using a CLIA level assay of biallelic inactivation of BRCA1, BRCA2, PALB2, FANCA or biallelic inactivation or monoallelic inactivating mutation of ATM. It is anticipated that the majority of patients will be germline carriers of a pathogenic variant of BRCA1, BRCA2 or ATM. Other germline mutations will be considered at investigator's discretion.
• Must be candidates for radical prostatectomy and considered surgically resectable by urologic evaluation.
• No evidence of metastatic disease or nodal disease as determined by radionuclide bone scans and computed tomography (CT)/magnetic resonance imaging (MRI); non-pathological lymph nodes must be less than 20 mm in the short (transverse) axis.
• Provided written authorization for use and release of health and research study information.
• Hemoglobin \>= 10.0 g/dL with no blood transfusion in the past 28 days.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 28 days prior to administration of study treatment).
• Platelet count \>= 100 x 10\^9/L (within 28 days prior to administration of study treatment).
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =\< 5 x ULN (within 28 days prior to administration of study treatment).
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of \>= 51 mL/min (within 28 days prior to administration of study treatment).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Patients must have a life expectancy \>= 16 weeks.
• Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Any previous treatment with PARP inhibitor, 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) curatively treated with no evidence of disease for \>= 5 years.
• Resting electrocardiogram (ECG) with corrected QT interval (QTc) \> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.
• Patients receiving any systemic chemotherapy, hormonal therapy or radiotherapy.
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML).
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any 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, 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.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
• Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
• Previous allogenic bone marrow transplant or cord blood transplantation.

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Bruce Montgomery, PI
• Organization: University of Washington

rbmontgo@uw.edu

206-598-0860

Study Officials

• Robert Montgomery

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: June 5, 2018
• First Posted: June 27, 2018
• Study Start: September 11, 2018
• Primary Completion: May 31, 2019
• Study Completion: July 3, 2019
• Last Updated: September 21, 2020
• Results First Posted: September 21, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)