Recurrent ovarian, tubal or peritoneal cancer MedDRA version: 20.0 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: TECENTRIQ
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: ATEZOLIZUMAB
Other descriptive name: TECENTRIQ
Concentration unit: mg/ml millig
Sponsors
Grupo Español de Investigación en Cáncer de Ovario (GEICO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients = 18 years old 2. Life expectancy =3 months 3. Signed informed consent and ability to comply with treatment and follow-up 4. Histologically confirmed diagnosis (cytology alone excluded) of high- grade serous or endometrioid ovarian, primary peritoneal or tubal carcinoma. In addition, mixed histologies with predominat high grade serous or endometrioid, or undifferentiated adenocarcinoma of the ovary are allowed 5. BRCA mutational status is known (germline or somatic) 6. Relapsed disease more than 6 months after the last platinum dose: 7. No more than 2 prior lines of chemotherapy are allowed, and the last one must contain a platinum-based regimen 8. At least one measurable lesion to assess response by RECIST v1.1 criteria. 9. Mandatory de novo tumor biopsy (collected within 3mths prior to randomization) sent to central laboratory as a FFPE sample for PD-L1 status determination for randomization 10. Two additional tumour samples are needed. Archival tumor sample must be available for exploratory PD-L1 testing in archival tissue and archival or fresh tissue sample for biomarkers must also be available. 11. Performance status determined by ECOG score of 0-1 12. Patients must have normal organ and bone marrow function: - Haemoglobin =10.0 g/dL - Absolute neutrophil count (ANC) =1.5 x 109/L - Lymphocyte count =0.5 × 109/L - Platelet count =100 x 109/L - Total bilirubin =1.5 x institutional upper limit of normal (ULN) - Serum albumin =2.5 g/dL - Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =2.5 x ULN, unless liver metastases are present in which case they must be =5 x ULN - Serum creatinine =1.5 x institutional ULN or calculated creatinine clearance = 30 mL/min using the Cockcroft-Gault equation - Patients not receiving anticoagulant medication must have an International Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN. 13. Negative Test Results for Hepatitis 14. Toxicities related to previous treatments must be recovered to =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Non-epithelial tumor of the ovary, the fallopian tube or the peritoneum 2.Ovarian tumors of low malignant potential or low grade 3.Other malignancy within the last 5 years except curatively treated non-melanoma skin cancer, in situ cancer of the cervix and ductal carcinoma in situ (DCIS) 4.Major surgery or patients who have not completely recovered from the effects of any major surgery at randomization 5.Core biopsy or other minor surgical procedure. 6.Administration of other CT drugs, anticancer therapy or anti-neoplastic hormonal therapy, or TTT with other investigational agents or devices 7.Palliative radiotherapy 8.Current or recent chronic use of aspirin or clopidogrel 9.Clinically significant cardiovascular disease 10.Resting ECG with QTc >470 msec on 2 or more time points within a 24 h period or family history of long QT syndrom 11.LVEF defined by MUGA/ECHO below the institutional lower limit of normal 12.History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory in case of suspected brain metastases 13.History or evidence upon neurological examination of central nervous system (CNS) disorders 14.Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease 15.Uncontrolled tumor-related pain 16.Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures 17.Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab 18.Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for TTT related complications 19.Pregnant or lactating women. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study TTT 20.Simultaneously receiving therapy in any interventional clinical trial. 21.Prior treatment with CD137 agonists or immune checkpoint stimulating or blockade therapies, such as anti-PD1, anti-PDL1 or anti-CTLA4 therapeutic antibodies 22.Treatment with systemic immunostimulatory agents 23.Treatment with systemic corticosteroids or other systemic immunosuppressive medications 24.History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrom, Guillain-Barré syndrom, multiple sclerosis, vasculitis, or glomerulonephritis. 25.History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis. 26.Immunocompromised patients, e.g., patients who are known to be serologically positive for HIV 27.Signs or symptoms of infection within 4 wks prior to Cycle 1, Day 1 28.Active Tuberculosis 29.Administration of a live, attenuated vaccine or anticipation that it will be administered at any time during the treatment period of the study or within 5 months after the final dose of atezolizumab 30.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 31.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hams
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine whether the addition of atezolizumab to carboplatin-based chemotherapy followed by maintenance niraparib improves progression-free survival (PFS) compared to placebo combined with carboplatin-based chemotherapy followed by maintenance niraparib, in patients with relapsed epithelial ovarian, fallopian tube, or peritoneal cancer after a platinum treatment free interval (TFIp) of at least 6 months (platinum-sensitive).;Secondary Objective: - Evaluate overall survival - Evaluate time from randomization to first subsequent therapy or death (TFST) - Evaluate time from randomization to second subsequent therapy or death (TSST) - Evaluate time from randomization to second progression or death (PFS2) - Assess the safety and tolerability of atezolizumab treatment - Determine the impact of atezolizuma on patient-reported abdominal symptoms of ovarian cancer. - Evaluate patient-reported outcomes of function and health related quality of life associated with atezolizumab - Evaluate the ORR - Evaluate the duration of response - Evaluate the PFS in patients in complete or partial response - Evaluate the efficacy of atezolizumab versus placebo according to BRCA status - Characterize the PK of atezolizumab and determine the incidence of ATAs - To evaluate the efficacy of atezolizumab compared to placebo in the PD-L1 negative and PD-L1 positive subgroups;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: From randomization until progression based on investigator assessment determined by RECIST (version v1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS), defined as the observed length of life from entry into the study (day of randomization) to death from any cause, or the date of last contact if patient alive - Time from randomization to first subsequent therapy or death (TFST) - Time from randomization to second subsequent therapy or death (TSST) - Time from randomization to second progression or death (PFS2) - Frequency and severity of adverse events as assessed by CTCAE version 4.03 for the regimens administered on this study - Clinically-meaningful improvement in patient-reported abdominal pain or bloating, defined as a 10-point decrease from the baseline score on either of the two items of the EORTC QLQ-OV28 abdominal/GI symptom scale (items 31 and 32) - Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30 - Objective Response Rate (ORR) as assessed by RECIST v1.1 during the chemotherapy phase and during the maintenance phase - Duration of response (DOR) by RECIST v1.1 - PFS from start of the maintenance phase (period from start of maintenance treatment until disease progression, death or date of last contact) assessed by the investigator according to RECIST v1.1 criteria, in all patients receiving maintenance treatment as well as in the subgroup of patients with CR/PR of SD after completing chemotherapy - Relationship of primary and secondary endpoint outcomes with BRCA mutational status and other stratification factors - Serum concentration (Cmin and Cmax) of atezolizumab at specified timepoints. Incidence of ATAs during the study relative to the prevalence of ATAs at baseline - Mean and mean changes from the baseline score in disease and/or treatment-related symptoms by cycle and | — |
Countries
Belgium, France, Germany, Italy, Spain
Contacts
Public ContactJavier Sanchez
Grupo Español de Investigación en Cáncer de Ovario (GEICO)
Outcome results
None listed