Newly Diagnosed Advanced Epithelial Ovarian Cancer MedDRA version: 18.1 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Debio 1143
Product Code: Debio 1143
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NA
Current Sponsor code: Debio 1143
Other descriptive name: Debio 1143
Concentration unit: mg
Sponsors
Debiopharm International SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women ? 18 years ? 70 years. 2. Patient with newly diagnosed, histologically confirmed (cytology alone excluded) high-grade serous ovarian cancer and high-grade endometrioid ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma. For patients with endometrioid cancer, only grade 3 defined by morphological features and immunohistochemical staining are eligible. 3. Documented FIGO stage IIIC-IV confirmed by laparoscopy (or mini-laparotomy) and imaging AND unsuitable for primary complete cytoreductive surgery. 4. Medically fit to undergo surgical cytoreduction after 4 cycles of neoadjuvant chemotherapy. 5. Eligible for carboplatin and paclitaxel chemotherapy. 6. Tumour biopsy sample for exploratory analysis. 7. ECOG performance score 0-2. 8. Life expectancy of at least 6 months in the best judgement of the investigator. 9. Minimum of one measurable tumour lesion, according to the RECIST 1.1 criteria (measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ? 20 mm by chest x-ray, as ? 10 mm with CT scan, or > 10 mm with calipers by clinical exam. Lymph nodes with a short axis ? 15 mm are considered to be measurable and assessable as target lesions). 10. Adequate bone marrow, renal and liver function: calculated creatinine clearance ? 50 mL/min as determined by the modified Cockcroft method; absolute neutrophil count ? 1500/?L, platelets ? 100000/?L, haemoglobin ? 9 g/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: 1. History of another active malignancy within the preceding 3 years, except for adequately treated carcinoma in situ of the cervix, breast, and non-melanomatous skin. 2. Mucinous, clear cell, and carcinosarcoma histologies. 3. Clinical evidence of brain or leptomeningeal metastases. 4. Serious disabling disease contraindicating cytoreductive surgery such as, but not limited to, New York Heart Association (NYHA) grade 3/4 congestive heart failure and severe pulmonary disease. 5. Major surgery within 28 days prior to the first dose of study treatment and not fully recovered to baseline or to a stable clinical status. 6. Human immunodeficiency virus (HIV) infection (testing required) 7. Known history of HBV or HCV (testing not required in the absence of clinical findings or suspicion). 8. Pre-existing sensory or motor neuropathy NCI-CTCAE v 4.03 ? 2. 9. Any psychological familial, sociological or geographical condition potentially preventing compliance with the study protocol schedule. 10. Prior treatment with an inhibitor of apoptosis protein (IAP) inhibitors. 11. Known allergic reaction triggered by Debio 1143 or its excipients. 12. Use or requirement for use of aspirin or aspirin-containing products with > 160 mg of aspirin per day. 13. Concurrent treatment with prohibited medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the antitumour activity according to RECIST 1.1 criteria of paclitaxel + carboplatin with or without Debio 1143 at the end of neoadjuvant treatment (prior to interval debulking surgery) in patients with newly diagnosed epithelial ovarian cancer.;Primary end point(s): Response Rate (RR) according to RECIST 1.1 criteria at the end of 4 cycles of neoadjuvant treatment and prior to interval debulking surgery as determined by central independent radiology committee;Secondary Objective: To determine the rate of optimal surgical cytoreduction at interval debulking surgery To determine the rate of radiological complete response at the end of neoadjuvant treatment and after debulking surgery/ the rate of complete pathological response To assess tumour response to paclitaxel+carboplatin with or without Debio1143 as measured by CA125 tumour marker during the neoadjuvant treatment and after debulking surgery/ the safety and tolerability of Debio1143 when given in combination with paclitaxel+carboplatin/ the duration of surgical intervention and the rate of perioperative morbidity To determine the rate of postoperative mortality/ the discharge time from hospital To investigate the Exposure/Response of Debio 1143 when combined with paclitaxel and carboplatin, based on PK disposition relationship with any pharmacological, safety, and/or efficacy markers To confirm that paclitaxel exposure in the Debio 1143 treatment group is comparable to the control group;Timepoint(s) of evaluation of this end point: At the end of 4 cycles of neoadjuvant treatment and prior to interval debulking surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Rate of complete cytoreduction (sCR), defined as no macroscopic residual tumour at time of interval debulking surgery -Rate of radiological CR as assessed by RECIST 1.1 at the end of neoadjuvant treatment (prior to interval debulking surgery) and after debulking surgery -Rate of response rate at the end of neoadjuvant treatment and after interval debulking surgery (EOS) -Rate of complete pathological response (pCR) defined as no residual invasive cancer at the time of debulking -Response rate measured by CA-125 tumour marker during the neoadjuvant treatment and after debulking surgery as assessed by GCIG criteria -Incidence of AEs and SAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03 criteria and extent of treatment exposure -Safety and tolerability of Debio 1143 when given in combination with paclitaxel + carboplatin as assessed by laboratory values, vital signs, ECG, and ECOG PS -Rate of perioperative serious complications within the first 28 days such as grade 3 to 5 hemorrhage/bleeding during surgery or postoperative requiring at least 2 units transfusion of red blood cells, vascular events (thrombosis/embolism), infections requiring IV antibiotics/antifungal or antiviral intervention, gastrointestinal fistula, urine fistula, etc -Rate of postoperative death (0.05, total body clearance (CL), and any other PK parameter as deemed appropriate. Adequate paclitaxel exposure will be evaluated by comparing AUC and TC>0.05 between both study arms, notably in the PK subset of 8 and 15 consecutive patients approximately by treatment arm. o Carboplatin PK parameter: AUC of free platinum and any other PK parameter as deemed appropriate. -Exposure/Response relationship based on the exposure measure (i.e., parameter characterizing drug input into the body) and the response measure (i.e. direct measures of the pharmacological effect of the drug by PDy marker (MCP1, CK-M30), efficacy marker, sa | — |
Countries
Belgium, France, Italy, Spain
Contacts
Public ContactProject Manager
INC
Outcome results
None listed