Prostate Adenocarcinoma Without Neuroendocrine DifferentiationPhase 2NCT03570476

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

A Phase 2 study testing Olaparib and Radical Prostatectomy in people with Prostate Adenocarcinoma Without Neuroendocrine Differentiation and Stage I Prostate Cancer AJCC v8, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Prostate Adenocarcinoma Without Neuroendocrine Differentiation, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8
What is being tested?: Olaparib and Radical Prostatectomy
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: 11 Sep 2018to 3 Jul 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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).

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Open-Label, Pilot Study of Olaparib as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer

Read the detailed description

PRIMARY OBJECTIVE:

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:

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.

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
Being tested: Olaparib, Radical Prostatectomy
Medical subject headings: Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OlaparibDrug
Also called AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281
Given orally
Radical ProstatectomyProcedure or surgery
Also called Prostatovesiculectomy
Undergo surgery

Study groups in NCT03570476
Study group	Role	What they receive
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. Receives: Drug: Olaparib; Procedure: Radical Prostatectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: Up to 30 days after the last dose of olaparib

Secondary outcomes (2)

Rate of Positive Surgical Margins
The rate of detectable tumor in pathology specimens obtained at prostatectomy.
Measured: At time of prostatectomy (at 12 weeks)
Stage of Disease
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
Measured: At time of prostatectomy (at 12 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 20183 Jul 2019

First posted27 Jun 2018
Study start11 Sep 2018
Primary completion31 May 2019
Study completion3 Jul 2019

Why it stopped: Terminated due to slow accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Prostate Adenocarcinoma Without Neuroendocrine DifferentiationStudies of the same condition, open and under way.
More trials run by University of WashingtonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03570476
Sponsor's protocol ID: 9985
Other IDs: NCI-2018-00977, 9985, P30CA015704, RG1718008
Status last verified: Jul 2020
First submitted: 5 Jun 2018
Last updated: 21 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 21 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-Label, Pilot Study of Olaparib as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer
ClinicalTrials.gov ID: NCT03570476
Acronym / sponsor ID: 9985
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
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Terminated due to slow accrual
Enrolment: 2 participants (actual)
Lead sponsor: University of WashingtonUniversity, hospital or other
Collaborators: National Cancer Institute (NCI), AstraZeneca
Study start: 11 Sep 2018 (actual)
Primary completion: 31 May 2019 (actual)
Study completion: 3 Jul 2019 (actual)
First posted: 27 Jun 2018 (actual)
Results: Posted 21 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVE:

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:

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (olaparib, radical prostatectomy)	Experimental	Drug: Olaparib, Procedure: Radical ProstatectomyParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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.

Key exclusion criteria (16 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OlaparibAlso: AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Given orally	Drug	Treatment (olaparib, radical prostatectomy)
Radical ProstatectomyAlso: ProstatovesiculectomyUndergo surgery	Procedure or surgery	Treatment (olaparib, radical prostatectomy)

Primary outcome

Pathologic Complete Response (pCR) Rate
Time frame: 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).
Number of Participants With Adverse Events
Time frame: Up to 30 days after the last dose of olaparib
Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).

2 secondary outcomes

Rate of Positive Surgical Margins
Time frame: At time of prostatectomy (at 12 weeks)
Stage of Disease
Time frame: At time of prostatectomy (at 12 weeks)

Results and safety

Results posted to the registry on 21 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment (Olaparib, Radical Prostatectomy)	2	2

Primary outcome: Pathologic Complete Response (pCR) Rate

Time frame: At time of prostatectomy (at 12 weeks). Count of participants. Unit: Participants

Measure	Treatment (Olaparib, Radical Prostatectomy) n = 2
Value	0

Primary outcome: Number of Participants With Adverse Events

Time frame: Up to 30 days after the last dose of olaparib. Count of participants. Unit: Participants

Measure	Treatment (Olaparib, Radical Prostatectomy) n = 2
Value	0

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 4 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Olaparib, Radical Prostatectomy)	0 of 2 (0%)	0 of 2 (0%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert Montgomery principal investigator

Fred Hutch/University of Washington Cancer Consortium

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (pCR) Rate (time frame: At time of prostatectomy (at 12 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03570476.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2020.