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Biochemically Recurrent Prostate CarcinomaPhase 2NCT04336943

Durvalumab and Olaparib for the Treatment of Prostate Cancer in Men Predicted to Have a High Neoantigen Load

A Phase 2 study testing Durvalumab, Olaparib and Quality-of-Life Assessment in people with Biochemically Recurrent Prostate Carcinoma and Prostate Adenocarcinoma, 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 durvalumab and olaparib work in treating prostate cancer in men predicted to have specific genetic mutations (a high neoantigen load). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Durvalumab, Olaparib and Quality-of-Life Assessment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
13 Apr 2021to 6 Jun 2025
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

  • Histologic confirmation of adenocarcinoma of the prostate
  • The patient must have received definitive local therapy for prostate cancer, consisting of either radiation therapy and/or prostatectomy (salvage or adjuvant radiation post-prostatectomy is not exclusionary)
  • PSA must be >= 2 ng/ml if received only prior definitive radiation (no PSA threshold required if prior prostatectomy was performed) with a PSA doubling time (PSADT) =< 10 months:
  • PSADT calculation must include all recorded PSA values > 0.2 ng/ml over the past 6 months prior to randomization, with a minimum of 3 values spaced at least 2 weeks apart, with each included value preferably measured at the same laboratory. PSA values obtained prior to localized therapy will be excluded
  • The calculation of PSADT is based on the natural log of PSA
  • Prior salvage radiation or not a candidate for localized salvage radiation due to subject preference or clinical assessment based upon disease characteristics and/or subject co-morbidities
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  • Prior hormonal therapy (i.e. androgen deprivation therapy) when given as neoadjuvant/concurrent/adjuvant therapy along with definitive radiation is allowed, provided this was stopped >= 6 months prior to starting treatment per protocol AND testosterone is >= 150 ng/dl
  • No evidence of metastatic disease on imaging by whole body bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 6 weeks before study therapy start day. PSMA positron emission tomography (PET) or fluciclovine scan within 6 weeks of start day may substitute other imaging studies.
  • Patients with oligometastatic disease (i.e. =< 3 sites) detectable on advanced imaging only (e.g. PSMA or fluciclovine PET) are eligible
  • Abdominal or pelvic lymph nodes measuring =< 2 cm in short axis are allowed
  • Biomarker positive:
  • Biallelic CDK12 inactivating mutations as documented using a clinical grade sequencing assay performed in a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) certified laboratory or
  • MMRd/MSI-high as documented using a clinical grade assay performed in a CLIA/CAP certified laboratory or
  • Loss of function mutations in homologous recombination genes (i.e. homologous recombination deficiency; HRD) as documented using a clinical grade sequencing assay performed in a CLIA/CAP certified laboratory. Homologous recombination genes include, but not limited to BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51D, NBN, GEN1, RAD51C, MRE11A, BRIP11A, FAM175A.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
  • Age > 18 years at time of study entry.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)
  • Absolute neutrophil count (ANC) be >= 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)
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN (within 28 days prior to administration of study treatment)
  • Patient must have creatinine clearance (CL) >= 51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (within 28 days prior to administration of study treatment)
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  • Patients must have a life expectancy >= 16 weeks
  • Body weight > 30 kg
  • Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential

Who cannot join

  • Prior chemotherapy for prostate cancer, unless done in the neoadjuvant setting, and if the last dose was > 6 months prior to enrollment
  • Any prior treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • Any prior treatment with a PARP inhibitor, including olaparib
  • History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease >= 3 years before the first dose of durvalumab and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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  • Adequately treated carcinoma in situ without evidence of disease
  • History of leptomeningeal carcinomatosis
  • Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the treating physician (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fridericia [QTcF] prolongation > 470 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the study physician
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
  • 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, extensive bilateral lung disease on high resolution computed tomography (HRCT) scan, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea 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 with uncontrolled human immunodeficiency virus (HIV). HIV+ patients will be allowed on the study if on highly active antiretroviral therapy (HAART) and disease is controlled: CD4 >= 350 cell/mcl, undetectable viral load, and no prophylactic (PPX) antibiotics
  • Note: HIV screening is not required to be eligible for this study
  • Active infection including tuberculosis (TB testing only performed if deemed necessary per standard clinical practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the sponsor investigator
  • Patients with celiac disease controlled by diet alone
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab
  • Patients receiving any chemotherapy, immunotherapy, biologic, radiotherapy or hormonal therapy for cancer treatment concurrently or within 3 weeks of study treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is acceptable
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
  • 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 study treatment is 2 weeks
  • Concomitant use of known strong (e.g. phenobarbital, enzalutamide, 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 study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Participation in another clinical study with an investigational product administered in the last 3 months
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) or supportive care, while on the clinical study or during the follow-up period of this interventional study
  • Patients with a known hypersensitivity to olaparib or durvalumab or any of the excipients of the product
  • Involvement in the planning and/or conduct of the study

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: Durvalumab (MEDI4736) and Olaparib (AZD2281) for Treatment of Biochemically Recurrent Prostate Cancer in Men Predicted to Have a High Neoantigen Load: A Multicenter Pilot Study

This phase II trial studies how well durvalumab and olaparib work in treating prostate cancer in men predicted to have specific genetic mutations (a high neoantigen load). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving durvalumab and olaparib may kill more tumor cells in patients with prostate cancer predicted to have a high neoantigen load.

Read the detailed description

OUTLINE:

All patients receive durvalumab IV over 1 hour on day 1 of each cycle, total 6 cycles. Starting cycle 4, patients with CDK12 mutations and mismatch repair deficiency (MMRd)/microsatellite instability (MSI)-high will also receive olaparib orally (PO) twice daily (BID) on days 1- 28 of cycles 4-6. Patients with homologous recombination mutation will also receive olaparib PO BID on days 1-28 of cycles 1-6. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 weeks, and then every 12 weeks to complete 24 months (at 9, 12, 15, 18, 21 and 24 months).

Being tested
Durvalumab, Olaparib, Quality-of-Life Assessment, Questionnaire Administration

What participants receive

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

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU-0059436

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04336943
Study groupRoleWhat they receive
Treatment (durvalumab, olaparib)ExperimentalAll patients receive durvalumab IV over 1 hour on day 1 of each cycle. Patients with CDK12 mutation and MMRd/MSI-high also receive olaparib PO BID on days 1- 28 of cycles 3-6. Patients with homologous recombination mutation also receive olaparib PO BID on days 1-28 of cycles 1-6. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Durvalumab; Drug: Olaparib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

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

  1. Undetectable Prostate Specific Antigen (PSA)

    Will assess if patients achieve undetectable PSA for post-prostatectomy patients (including those that also received salvage radiation) or PSA < 0.5 ng/ml for post-definitive radiation patients.

    Measured: At 12 months after initiation of therapy

Secondary outcomes (3)

  1. PSA50 Response

    A descriptive summary (including the percentage and 90% confidence interval [CI]) of PSA50 response rate (proportion of patients with a decline in PSA > 50% from baseline) will be provided at 3- and 6-month timepoints. The response rate will be reported with exact binomial two-sided 90% CI.

    Measured: At 3 and 6 months

  2. Change in Quality of Life: RANDSF-36

    RAND 36-Item Short Form (RANDSF-36) assesses physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, general health perceptions, and perceived change in health with a total score range of 0-100. The total score from all of the questions answered is divided by the total number of the questions answered yielding a global score from 0-100, with a higher score reflecting a better QoL. Mean difference in total average score is reported. Since the same treatment is used for all groups, we are reporting the data for RANDSF-36 in aggregate. Because this study terminated prematurely, the small number of enrolled subjects also preclude our ability to break this data at by subgroups.

    Measured: At the time of enrollment and then every three months, with the last assessment at 12 months.

  3. Change in Quality of Life: IIEF

    International Index of Erectile Function (IIEF-5) is a diagnostic tool for erectile dysfunction, with a total score range of 5-25, with the lowest score indicating a higher degree of dysfunction. The mean difference in total score is reported. Since the same treatment is used for all groups, we are reporting the data for RANDSF-36 in aggregate. Because this study terminated prematurely, the small number of enrolled subjects also preclude our ability to break this data at by subgroups.

    Measured: At the time of enrollment and then every three months, with the final measurement after 12 months.

Timeline

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

  1. First posted7 Apr 2020
  2. Study start13 Apr 2021
  3. Primary completion20 Jun 2024
  4. Study completion6 Jun 2025

Why it stopped: Slow accrual

Resources

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04336943
Sponsor's protocol ID
RG1007001
Other IDs
NCI-2020-01860, 10509
Status last verified
Jul 2025
First submitted
3 Apr 2020
Last updated
11 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, Olaparib and Quality-of-Life Assessment in people with Biochemically Recurrent Prostate Carcinoma and Prostate Adenocarcinoma, run by University of Washington at 1 site in United States.

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 27 inclusion and 39 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 11 Aug 2025. 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 11 Aug 2025). 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?

Undetectable Prostate Specific Antigen (PSA) (time frame: At 12 months after initiation of therapy). 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 NCT04336943.

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 11 Aug 2025.

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