advanced ovarian cancer MedDRA version: 20.0 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10070907 Term: Ovarian cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853914
Current Sponsor code: MK 3475
Other descriptive n
Sponsors
ARCAGY-GINECO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Be willing and able to provide written informed consent for the trial. 2.Woman 18 and = 75 years old on day of signing informed consent 3.Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma with the exception of clear cell, mucinous histology. Histolo-gy should be obtained by laparoscopy (or by laparotomy). 4.High grade serous or endometrioid (see appendix 1 bis) 5.Advanced FIGO stage IIIC to IV patient not able to receive primary debulking surgery for whichneo adjuvant chemotherapy with carboplatin and paclitaxel is recommended. ( Patients with extra abdominal metastasis (FIGO 2014 Stage IV) can be included in case of completely resectable metastasis. 6.Primary debulking surgery denied and maximum surgical effort of cytoreduction with the goal of no residual disease planned as interval debulking surgery(i.e. Sugarbaker index less than 30) 7.Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care following cytoreductive surgery. 8. Debulking surgery anticipated in a center with excellence. 9. ECOG performance status (PS) = 2. 10. Life expectancy of at least 6 months, 11. Interval between diagnosis and enrolment (informed consent) = 8 weeks, 12. Be willing to provide blood, and tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) prior to initiation of treatment on Day 1. 13. Demonstrate adequate organ function as defined, all screening labs should be performed within 7 days before randomization. 14. Adequate hematological laboratory value: • Absolute neutrophil count (ANC) : =1,500/mm3 • Platelets : =100,000/mm3 15. Hemoglobin : =9 g/ Adequate renal laboratory value: Serum creatinine OR Measured or calculated creatinine clearance a (GFR can also be used in place of creatinine or CrCl) =1.5 X upper limit of normal (ULN) OR =60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (Creatinine clearance is calculated according to Cockcroft formula or to MDRD formula for patients older than 65 years-old. Glomerular filtration rate or creatinine clearance according to MDRD formula is: GFR = 186 x (creatinine (µmol/l) x 0,0113)-1,154 x age- 0,203 x 0.742.) 16. Adequate hepatic laboratory value: • Serum total bilirubin: = 1.5 X ULN OR • Direct bilirubin: = ULN for subjects with total bilirubin levels > 1.5 ULN • AST (SGOT) and ALT (SGPT): = 2.5 X ULN OR = 5 X ULN for subjects with liver metastases 17.Adequate coagulation laboratory value: • International Normalized Ratio (INR) or Prothrombin Time (PT) : =1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants • Activated Partial Thromboplastin Time (aPTT): =1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 18.Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 19.Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
Exclusion criteria
Exclusion criteria: 1. Histological diagnosis of malignant tumor of non-epithelial origin (e.g. germ cell tumor, sex cord-stromal tumor) of the ovary, the fallopian tube or peritoneum or borderline tumor of the ovary (tumor of low malignant potential). 2. Patients with extra abdominal metastasis (FIGO 2014 Stage IV) not completely resectable, as e.g. multiple parenchymal lung metastases (preferably histologically proven), non resectable lymph node metastases, brain metastases. 3. Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy), 4. Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target volume that would bear the risk of increased toxicity of chemotherapy, 5. Serious illness or concomitant non-oncological disease such as neurologic, cardiologic (ie. congestive heart failure > NYHA II), psychiatric or infectious disease, active ulcers (gastroin-testinal tract, skin) or a laboratory abnormality that may Increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study, 6. Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of severe hy-persensitivity reactions to paclitaxel or platinum-containing compounds and their excipients, or other drugs formulated with Polyoxyl 35Is currently participating and receiving study ther-apy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 7. Diagnosis of immunodeficiency or receiving prolonged period of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 8. Known history of active Bacillus Tuberculosis (TB) 9. Hypersensitivity to pembrolizumab or any of its excipients. 10. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not re-covery (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 11. Known additional malignancy that is progressing or requires active treatment. Exceptions in-clude basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has under-gone potentially curative therapy or in situ cervical cancer. 12. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded re-gardless of clinical stability. 13. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 14. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 15. History of Human Immunodeficiency Virus (HIV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of neoadjuvant pembrolizumab and chemo-therapy or chemotherapy alone measured by the complete resection rate after interval debulking surgery. Complete resection will be defined as the removal of all macroscopic residual tumor (Com-plete Cytoreduction score = 0).;Secondary Objective: •To evaluate the efficacy of the addition of pembrolizumab to chemotherapy assessed by : oThe Objective Response Rate at the time of interval debulking surgery (after 4 neo ad-juvant cycles) using RECIST 1.1 criteria oThe rate of the pCR oThe Best Overall Response to the global strategy of interval debulking surgery + chemo-therapy +/- Pembrolizumab assessed by CT-Scan (using RECIST 1.1) at the end of treat-ment visit & before interval surgery?. oThe Progression-Free Survival (PFS) using RECIST 1.1 criteria oBiological Progression-Free Interval (PFIBIO), by serum Ca125 measured according to the GCIG criteria oThe overall survival •To assess the safety profile of neo adjuvant and adjuvant pembrolizumab when combined with standard of care, according to NCI CTC-AE v4.03. •To assess the Post-operative mortality •To assess the Post-operative morbidity according to modified Clavien Dindo scoring. ;Primary end point(s): The primary objective is to evaluate the efficacy of neo adjuvant pembrolizumab and chemotherapy or chemo-therapy alone measured by the complete resection rate after interval debulking surgery. Complete resection will be defined as the removal of all macroscopic residual tumor (CC score = 0).;Timepoint(s) of evaluation of this end point: After interval debulking surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The Objective Response Rate assessed by CT-Scan (RECIST 1.1) at the time of interval debulking sur-gery (after 4 neo adjuvant cycles of treatment) • The rate of Pathologic Complete Response (pCR) after surgery • The best response rate • The Progression-Free Survival (PFS) • Biological Progression-Free Interval (PFIBIO), measured according to the GCIG criteria ( • Overall survival (OS) • The Best Overall Response to the global strategy of interval debulking surgery + chemotherapy +/- Pembrolizumab (MK-3475) assessed by CT-Scan (using RECIST 1.1) at the end of treatment visit. To assess the safety profile of neo adjuvant and adjuvant pembrolizumab when combined with standard of care, according to NCI CTC-AE v4.03. • To assess Post-operative mortality • To assess Post-operative morbidity according to modified Clavien Dindo scoring Radiological responses will be assessed by the investigators, according to RECIST version 1.1. ;Timepoint(s) of evaluation of this end point: The Objective Response Rate assessed by CT-Scan (RECIST 1.1) • The rate of Pathologic Complete Response (pCR) after surgery • The best response rate • The Progression-Free Survival (PFS) • Biological Progression-Free Interval (PFIBIO), measured according to the GCIG criteria • Overall survival (OS) • The Best Overall Response assessed by CT-Scan (using RECIST 1.1) at the end of treatment visit. To assess the safety profile according to NCI CTC-AE v4.03. • To assess Post-operative mortality • To assess Post-operative morbidity according to modified Clavien Dindo scoring Radiological responses will be assessed by the investigators, according to RECIST version 1.1. | — |
Countries
France
Outcome results
None listed