Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

• Sponsor: University of Washington (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03570476
• Collaborator: National Cancer Institute (NCI) (NIH), AstraZeneca (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 9.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Olaparib; Procedure: Radical Prostatectomy	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To assess the pathological complete response rate following olaparib when administered as neoadjuvant therapy prior to prostatectomy in patients with localized prostate cancer containing homozygous or complementary deoxyribonucleic acid [DNA] repair deficiency.

SECONDARY OBJECTIVE:

1. To determine the rate of positive surgical margins, extracapsular extension, positive seminal vesicles and lymph nodes at the time of prostatectomy.

OUTLINE:

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.

After completion of study treatment, participants are followed up for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label, Pilot Study of Olaparib as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer
• Actual Study Start Date: Sep 11, 2018
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: Jul 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (olaparib, radical prostatectomy) 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; Given orally; Other Names: AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 ; Procedure: Radical Prostatectomy; Undergo surgery; Other Names: Prostatovesiculectomy

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response (pCR) Rate [At time of prostatectomy (at 12 weeks)]

   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).

2. Number of Participants With Adverse Events [Up to 30 days after the last dose of olaparib]

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

Secondary Outcome Measures

1. Rate of Positive Surgical Margins [At time of prostatectomy (at 12 weeks)]

   The rate of detectable tumor in pathology specimens obtained at prostatectomy.

2. Stage of Disease [At time of prostatectomy (at 12 weeks)]

   Pathology specimens obtained at prostatectomy will be assessed using the tumor, lymph node, and metastasis (TNM) staging system for prostate cancer. Stage Stage 2 represents patients with disease without evidence of extension outside of the prostate Stage 3 represents patients with disease which has penetrated the capsule of the prostate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.

Exclusion Criteria:

• 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.

• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)
• AstraZeneca

Investigators

• Principal Investigator: Robert Montgomery, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Informed Consent Form - Jan 14, 2019
• Study Protocol and Statistical Analysis Plan - Apr 23, 2020

More Information

Publications

None provided.

• Responsible Party: University of Washington
• ClinicalTrials.gov Identifier: NCT03570476
• Other Study ID Numbers: 9985; NCI-2018-00977; 9985; P30CA015704; RG1718008
• First Posted: Jun 27, 2018
• Last Update Posted: Sep 21, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Olaparib; Poly(ADP-ribose) Polymerase Inhibitors

Study Results

Participant Flow

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	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. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	Participants receive olaparib PO BID for 90 days in the absence of unacceptable toxicity. Beginning 1 day after last olaparib dose, participants undergo radical prostatectomy. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Overall Participants	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (11)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response (pCR) Rate
Description	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).
Time Frame	At time of prostatectomy (at 12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	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. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Measure Participants	2
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame	Up to 30 days after the last dose of olaparib

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	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. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Measure Participants	2
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Rate of Positive Surgical Margins
Description	The rate of detectable tumor in pathology specimens obtained at prostatectomy.
Time Frame	At time of prostatectomy (at 12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	Participants receive olaparib PO BID for 90 days in the absence of unacceptable toxicity. Beginning 1 day after last olaparib dose, participants undergo radical prostatectomy. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Measure Participants	2
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Stage of Disease
Description	Pathology specimens obtained at prostatectomy will be assessed using the tumor, lymph node, and metastasis (TNM) staging system for prostate cancer. Stage Stage 2 represents patients with disease without evidence of extension outside of the prostate Stage 3 represents patients with disease which has penetrated the capsule of the prostate
Time Frame	At time of prostatectomy (at 12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	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. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
Measure Participants	2
Stage 2	0 0%
Stage 3	2 100%

Adverse Events

Time Frame	4 months
Adverse Event Reporting Description	Adverse events were collected according to CTCAE version 5
Arm/Group Title	Treatment (Olaparib, Radical Prostatectomy)
Arm/Group Description	Participants receive olaparib PO BID for 90 days in the absence of unacceptable toxicity. Beginning 1 day after last olaparib dose, participants undergo radical prostatectomy. Olaparib: Given PO Radical Prostatectomy: Undergo surgery
All Cause Mortality
	Treatment (Olaparib, Radical Prostatectomy)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Treatment (Olaparib, Radical Prostatectomy)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Olaparib, Radical Prostatectomy)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.