Clinical trial NCT04417192: Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Lead sponsor: National Cancer Center Hospital East
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-06-04
Enrollment: 30
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study has 2 cohorts. Cohort 1 is Olaparib monotherapy Cohort 2 is Olaparib plus Pembrolizumab combination therapy
Primary purpose: TREATMENT

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.

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).

Eligibility 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 6 weeks
Secondary outcomes:
measure: The incidence of adverse events
timeFrame: Up to 30 days after the last dose
measure: Chemotherapy response score (CRS)
timeFrame: 6 months from the end of registration
measure: Progression-free survival (PFS)
timeFrame: 6 months from the end of registration
measure: Overall survival (OS)
timeFrame: 6 months from the end of registration
Other outcomes:
measure: Biomarkers
timeFrame: 2 years
measure: The change in tumor-infiltrating lymphocytes
timeFrame: 2 years
measure: The therapeutic effect
timeFrame: 2 years
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
Study officials:
References: