Clinical Trials /

Olaparib for the Treatment of Castration Resistant Prostate Adenocarcinoma

NCT04951492

Description:

This phase II trial investigates the effect of olaparib in treating patients with castration resistant prostate adenocarcinoma. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib for the Treatment of Castration Resistant Prostate Adenocarcinoma
  • Official Title: Olaparib in Prostate Cancer Patients With Evidence of Homologous Recombination Deficiency as Assessed Using an Integrated Genomic Signature

Clinical Trial IDs

  • ORG STUDY ID: RG1121519
  • SECONDARY ID: NCI-2021-06147
  • SECONDARY ID: RG1121519
  • NCT ID: NCT04951492

Conditions

  • Castration-Resistant Prostate Carcinoma
  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
OlaparibAZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Treatment (Olaparib)

Purpose

This phase II trial investigates the effect of olaparib in treating patients with castration resistant prostate adenocarcinoma. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      OUTLINE:

      Patients receive olaparib orally (PO) twice daily (BID). Cycles repeat every 28 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Olaparib)ExperimentalPatients receive olaparib orally (PO) twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Subject must be >= 18 years of age at the time of signing the informed consent form

          -  Individuals who have documented histologically confirmed adenocarcinoma of the
             prostate

          -  Subject must have evidence of castration resistant prostate cancer as evidenced by PSA
             progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate
             serum testosterone level (i.e. =< 50 mg/dL)

          -  PSA must be at least 2 ng/mL and rising on two successive measurements at least two
             weeks apart

          -  At least one lesion (measurable and/or non-measurable) that can be accurately assessed
             at baseline by computed tomography (CT) scan, magnetic resonance imaging (MRI), or
             positron emission tomography (PET) and is suitable for repeated assessment

          -  Must have progressed on abiraterone and/or a second-generation androgen receptor (AR)
             antagonist (i.e. enzalutamide, apalutamide, or darolutamide). If these were given in
             the hormone sensitive setting, patients must also have progressed on at least one
             prior approved therapy for CRPC

          -  Must have archival tissue available or be willing to undergo metastatic biopsy in
             order to perform next-generation deoxyribonucleic acid (DNA) sequencing and undergo
             whole exome sequencing

          -  Patient must have a positive LOH score on prior University of Washington (UW) OncoPlex
             testing

          -  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) >= 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 of >= 51 mL/min using the
             Cockcroft-Gault equation or based on a 24 hour urine test (within 28 days prior to
             administration of study treatment)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Patients must have an estimated life expectancy >= 16 weeks

          -  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

        Exclusion Criteria:

          -  As judged by the investigator, any evidence of serious and/or unstable pre-existing
             medical or psychiatric condition which in the investigator's opinion makes it
             undesirable for the patient to participate in the trial

          -  Other malignancy unless curatively treated with no evidence of disease for >= 5 years
             except: adequately treated non-melanoma skin cancer and non-muscle invasive bladder
             cancer

          -  Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible
             cardiac conditions, as judged by the investigator (e.g., unstable ischemia,
             uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval
             by Fridericia's formula [QTcF] prolongation > 500 ms, electrolyte disturbances, etc.),
             or patients with congenital long QT syndrome

          -  Persistent toxicities (> Common Terminology Criteria for Adverse Event (CTCAE) grade
             2) caused by previous cancer therapy, excluding alopecia

          -  Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
             suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)

          -  Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
             of brain metastases is not required. The patient can receive a stable dose of
             corticosteroids before and during the study as long as these were started at least 4
             weeks prior to treatment. Patients with spinal cord compression unless considered to
             have received definitive treatment for this and evidence of clinically stable disease
             for 28 days

          -  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, unstable spinal
             cord compression, superior vena cava syndrome, 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) and are not receiving active treatment or have
             a detectable viral load

          -  Patients with known active hepatitis (i.e. hepatitis B or C).

               -  Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen
                  (HBsAg) result. Patients with a past or resolved HBV infection (defined as the
                  presence of hepatitis B core antibody 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)

          -  Any previous treatment with PARP inhibitor, including olaparib

          -  Any previous treatment with platinum chemotherapy in the metastatic
             castration-resistant setting

          -  Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
             reasons) within 3 weeks prior to study treatment

          -  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 (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, 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 olaparib 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)

          -  Patients with a known hypersensitivity to olaparib or any of the excipients of the
             product

          -  Involvement in the planning and/or conduct of the study

          -  Judgment by the investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Lowest on-treatment prostate specific antigen (PSA)
Time Frame:At least 12 weeks of olaparib treatment
Safety Issue:
Description:Will be calculated along with 90% confidence intervals (CI) using Wilson's method. PSA changes will be presented as waterfall plots per Prostate Cancer Working Group 3 criteria recommendations.

Secondary Outcome Measures

Measure:Radiographic response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria. Radiographic responses will be presented as waterfall plots.
Measure:Radiographic progression free survival (PFS)
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method. Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
Measure:PSA PFS
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed by Prostate Cancer Working Group 3 criteria. Will be estimated using the Kaplan-Meier method. Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
Measure:Overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method. Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
Measure:Incidence and severity of adverse events
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed according to the National Cancer Institute- Common Terminology Criteria for Adverse Events version 4.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Last Updated

July 6, 2021