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Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer (OLAPem)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04417192
Recruitment Status : Not yet recruiting
First Posted : June 4, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Toru Mukohara, National Cancer Center Hospital East

Brief Summary:
To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV high-grade serous or Grade 3 endometrioid ovarian cancer with Homologous Recombination Deficiency (HRD) positivity.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Olaparib Drug: Pembrolizumab Phase 2

Detailed Description:
To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV high-grade serous or Grade 3 endometrioid ovarian cancer with HRD positivity. The first cohort (Olaparib monotherapy : 10 cases) will be evaluated for the presence or absence of immune cell activation, and the tumor reduction effect will be evaluated in the second cohort (Olaparib plus pembrolizumab combination therapy : 20 cases).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This study has 2 cohorts. Cohort 1 is Olaparib monotherapy Cohort 2 is Olaparib plus Pembrolizumab combination therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Efficacy and Safety of Preoperative Olaparib Monotherapy and Preoperative Olaparib Plus Pembrolizumab Combination Therapy in Patients With HRD-Positive Stage III or IV Advanced Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Cancer
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Olaparib or Olaparib Plus Pembrolizumab
Cohort 1 : Olaparib will be administered for 6 weeks before surgery. Cohort 2 : Olaparib and Pembrolizumab will be administered simultaneously for 2 cycles(6 weeks) before surgery.
Drug: Olaparib
Olaparib will be administered at a dose of 300mg as oral dose, twice a day.

Drug: Pembrolizumab
Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 6 weeks ]
    Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1.


Secondary Outcome Measures :
  1. The incidence of adverse events [ Time Frame: Up to 30 days after the last dose ]
    The incidences and types of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. Chemotherapy response score (CRS) [ Time Frame: 6 months from the end of registration ]
    To evaluate the effect of histopathological treatment on patients with serous carcinoma and metastasis to the omentum. The histopathological treatment effect is determined according to the chemotherapy response score (CRS)

  3. Progression-free survival (PFS) [ Time Frame: 6 months from the end of registration ]
    PFS is defined as the time from the first dose to the earlier of progression assessed by the Investigator per RECIST v. 1.1 (PD) or clinical criteria, or death due to any cause.

  4. Overall survival (OS) [ Time Frame: 6 months from the end of registration ]
    OS is defined as the time from the first dose to death due to any cause.


Other Outcome Measures:
  1. Biomarkers [ Time Frame: 2 years ]
    Relationship between the germline mutation and therapeutic effect

  2. The change in tumor-infiltrating lymphocytes [ Time Frame: 2 years ]
    Relationship between the change in tumor-infiltrating lymphocytes in tumor tissue before and after therapy, and the therapeutic effect

  3. The therapeutic effect [ Time Frame: 2 years ]
    Relationship between the Tumor Mutation Burden (TMB) and the therapeutic effect



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has given signed informed consent to participate in the clinical trial of her own will.
  2. Is aged 20 years or older on the day of signing the informed consent.
  3. Has been diagnosed with histologically confirmed, Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer by the International Federation of Gynecology and Obstetrics (FIGO) staging system (2014), with a histological type of high-grade serous or Grade 3 endometrioid carcinoma.
  4. Have measurable disease based on RECIST 1.1.
  5. Is a candidate for debulking surgery.
  6. Has an HRD-positive tumor.
  7. Has an ECOG Performance Status of 0 or 1.
  8. Laboratory test results within 21 days prior to enrollment have met the following organ function criteria. However, measurements within 14 days of blood transfusion or administration of granulocyte-colony stimulating factor (G-CSF) are excluded.

    • Neutrophil count ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • Hemoglobin ≥ 9.0 g/dL
    • Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min
    • T-Bil ≤ 2.0 mg/dL
    • ALT and AST ≤ 100 U/L (≤ 200 U/L if liver metastasis is present)
  9. A woman of childbearing potential must agree to use contraception after signing the informed consent, throughout the study period, and until at least 120 days following the last dose of the study drug

Exclusion Criteria:

  1. Has received previous allogeneic bone-marrow transplantation.
  2. Has concurrent interstitial lung disease/pneumonitis, or a history of (noninfectious) interstitial lung disease/pneumonitis that required treatment with steroids. Interstitial lung disease/pneumonitis includes radiation pneumonitis.
  3. Has received prior antitumor therapy (e.g., chemotherapy, molecular-targeted therapy, therapeutic antibody, endocrine therapy, immunotherapy, and investigational therapy).
  4. Has received surgery under general anesthesia within 28 days prior to enrollment. However, surgery to diagnose ovarian/fallopian tube/peritoneal cancer performed under general anesthesia is allowed.
  5. Has received radiation or radioactive isotope therapy within 28 days prior to enrollment.
  6. Has uncontrolled pericardial effusion, pleural effusion, or peritoneal effusion.
  7. Has a history of cerebral infarction, cerebral hemorrhage, or transient cerebral ischemia within 180 days prior to enrollment.
  8. Has a history of deep vein thrombosis or pulmonary embolism.
  9. Is receiving systemic glucocorticoid therapy or systemic immunosuppressive therapy.
  10. Has a history of autoimmune disease.
  11. Is infected with human immunodeficiency virus (HIV).
  12. Is infected with active* hepatitis B or hepatitis C.

    *: Active hepatitis B is defined as HBs antigen positive.

  13. Has a symptomatic infection within 14 days prior to enrollment.
  14. Has received a live vaccine within 28 days prior to enrollment.
  15. Has clinically critical cardiac disease (has a history of myocardial infarction or angina pectoris within 180 days prior to enrollment or has New York Heart Association [NYHA] class II or higher cardiac failure, uncontrolled arrhythmia, or QTc prolongation defined as QTc > 470 msec).
  16. Has active brain metastasis or a tumor causing spinal cord compression.
  17. Is pregnant or breastfeeding.
  18. Has a history of severe allergy, anaphylaxis, or hypersensitivity induced by humanized chimeric antibodies.
  19. Is allergic to biologics produced from Chinese hamster ovary (CHO) cells, carboplatin, or paclitaxel.
  20. Has a known or suspected active malignancy that is different from the disease of interest in the clinical trial or has a history of other malignancy within 3 years prior to enrollment. However, cutaneous basal cell carcinoma and cervical carcinoma in situ are not part of this exclusion criterion.
  21. Is unwilling to or unable to comply with the protocol.
  22. Is not eligible to enroll in the clinical trial based on the judgment by the Investigator or Sub-investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04417192


Contacts
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Contact: Kenichi Harano, MD +81-4-7133-1111 OLAPem_core@east.ncc.go.jp

Locations
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Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
Contact: Kenichi Harano, MD    +81-4-7133-1111    OLAPem_core@east.ncc.go.jp   
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, Japan
Contact: Kazuhiro Takehara, MD         
Kurume University Hospital
Kurume, Fukuoka, Japan
Contact: Shin Nishio, MD         
Sponsors and Collaborators
National Cancer Center Hospital East
Merck Sharp & Dohme Corp.
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Responsible Party: Toru Mukohara, Chief of Breast and Medical Oncology Division, National Cancer Center Hospital East
ClinicalTrials.gov Identifier: NCT04417192    
Other Study ID Numbers: EPOC1903
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pembrolizumab
Olaparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action