Clinical Trials /

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

NCT03570476

Description:

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. 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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer
  • Official Title: Open-Label, Pilot Study of Olaparib as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 9985
  • SECONDARY ID: NCI-2018-00977
  • SECONDARY ID: 9985
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03570476

Conditions

  • ATM Biallelic Inactivation
  • ATM Gene Mutation
  • ATM Monoallelic Inactivation
  • BRCA1 Biallelic Inactivation
  • BRCA1 Gene Mutation
  • BRCA2 Biallelic Inactivation
  • BRCA2 Gene Mutation
  • FANCA Biallelic Inactivation
  • Homologous Recombination Deficiency
  • PALB2 Biallelic Inactivation
  • PALB2 Gene Mutation
  • Prostate Adenocarcinoma Without Evidence of 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

Interventions

DrugSynonymsArms
OlaparibAZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Treatment (olaparib, radical prostatectomy)

Purpose

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. 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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 OBJECTIVES:

      I. 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 (PO) twice daily (BID) 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (olaparib, radical prostatectomy)ExperimentalParticipants 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

Eligibility Criteria

        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.

          -  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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (pCR) rate
Time Frame:At time of prostatectomy (at 12 weeks)
Safety Issue:
Description:Proportion 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).

Secondary Outcome Measures

Measure:Rate of positive surgical margins
Time Frame:At time of prostatectomy (at 12 weeks)
Safety Issue:
Description:The rate of detectable tumor in pathology specimens obtained at prostatectomy.
Measure:Stage of disease
Time Frame:At time of prostatectomy (at 12 weeks)
Safety Issue:
Description:Pathology specimens obtained at prostatectomy will be assessed using the tumor, lymph node, and metastasis (TNM) staging system for prostate cancer.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

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