E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ovarian cancer (OC), fallopian tube cancer (FTC), primary peritoneal cancer (PPC) |
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E.1.1.1 | Medical condition in easily understood language |
OC, FTC, and PPC are diseases in which cells from either ovary, fallopian tube, or lining of the abdominal cavity grow abnormally into cancer cells and spread |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of atezolizumab (Atezo) versus (vs) placebo (PL) in combination with paclitaxel (Pac)+ carboplatin (Carb)+ bevacizumab (Bev) in all OC, FTC, and PPC patients and in those with programmed death ligand-1 (PD-L1)−positive tumors
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy and duration of efficacy of Atezo vs PL in combination with Pac + Carb +Bev among patients with measurable residual disease in the primary surgery group •To determine the impact of Atezo vs PL in combination with Pac + Carb +Bev on patient-reported abdominal symptoms of OC, as measured by two items from the abdominal and gastrointestinal symptom scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Ovarian Cancer Module 28 (QLQ-OV28) •To evaluate patient-reported outcomes of function and health-related quality of life( HRQoL) associated with Atezo vs PL in combination with Pac + Carb +Bev as measured by the functional and HRQoL scales of the EORTC QLQ Core 30 (QLQ-C30)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Receive a histologic diagnosis of epithelial OC, FTC, or PPC fulfilling the following criteria: epithelial tumors histologically of Mullerian origin - Patients with Stage III or Stage IV who have gross residual disease after primary surgery or who will undergo neoadjuvant treatment and planned interval surgery after Cycle 3 - Eastern Cooperative Oncology Group performance status of 0, 1, or 2 - Life expectancy > 12 weeks - Adequate hematologic and end-organ function test results - On a stable anticoagulant regimen, if therapeutic anticoagulation is indicated - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that have a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study drug and 6 months after the last dose of Bev, Pac, or Carb, whichever is later - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including all patient-reported outcomes questionnaires - Availability of a representative formalin-fixed, paraffin-embedded tumor specimen (screening baseline tissue) in paraffin blocks or at least 20 unstained slides. - For patient enrolled in the extended China enrollment phase: residents in Mainland China, residents in Hong Kong and Taiwan of Chinese ancestry and enrolled at sites recognized by China FDA |
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E.4 | Principal exclusion criteria |
- Received a current diagnosis of borderline epithelial ovarian tumor - Recurrent invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer that was treated only with surgery - Non-epithelial ovarian tumors - Received prior radiotherapy to any portion of the abdomen or pelvis - Received prior chemotherapy for any abdominal or pelvic tumor, including neoadjuvant chemotherapy for ovarian, primary peritoneal or fallopian tube cancer - Received any hormonal, biological, and/or targeted therapy for epithelial ovarian, fallopian tube or primary peritoneal cancer - Synchronous primary endometrial cancer - Prior history of primary endometrial cancer, except if all of the mentioned conditions are met: Stage IA cancer, superficial myometrial invasion without lymphovascular invasion, and Grade < 3 or poorly differentiated subtypes which includes papillary serous, clear cell or other International Federation of Gynecological Oncologists Grade 3 lesions - With the exception of non-melanoma skin cancer and other specific malignancies as noted above, other invasive malignancies with any evidence of other cancers present within the last 5 years or previous cancer treatment that contraindicates this protocol therapy - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a screening chest computed tomography scan - Known hypersensitivity or allergy to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the Atezo and/or Bev formulations - Active or history of autoimmune disease or immune deficiency that includes but is not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener’s granulomatosis, Sjogren’s syndrome, Guillain-Barré syndrome, or multiple sclerosis - Active tuberculosis, positive test for HIV - Significant cardiovascular disease (e.g., New York Heart Association cardiac disease, myocardial infarction infarction or cerebrovascular accident within 3 months before initiation of study treatment, unstable arrhythmias, or unstable angina) - Inadequately-controlled hypertension - Prior history of hypertensive crisis or hypertensive encephalopathy - Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment - Current treatment with anti-viral therapy for HBV - Prior allogeneic bone marrow transplantation or solid organ transplant - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti−PD-1, anti−PD-L1, or anti-cytotoxic T-lymphocyte-associated protein 4 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment, systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment - History of hypertensive crisis or hypertensive encephalopathy, hemoptysis (Grade ≥ 2) within 1 month prior to initiation of study treatment, abdominal fistula or gastrointestinal perforation within 6 months prior to initiation of study treatment - Evidence of active bleeding, bleeding diathesis, coagulopathy, tumor that involves major vessels - History of leptomeningeal disease - History of Grade ≥ 4 venous thromboembolism - Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable prior to initiation of study treatment - Significant vascular disease within 6 months prior to initiation of study treatment - Evidence of active bleeding, bleeding diathesis, coagulopathy, tumor that involves major vessels, abdominal free air not explained by paracentesis or recent surgical procedure - Core biopsy or other minor surgical procedures within 7 days prior to the first dose of bevacizumab - Major surgical procedures within 28 days of first bevacizumab dose - Clinical signs of gastrointestinal obstruction requiring routine parenteral hydration, parenteral nutrition, or tube feeding - Grade >= 2 peripheral neuropathy as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 - Known history of severe hypersensitivity reactions to products that contain Cremophor® and severe allergic reactions to platinum-containing compounds
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Investigator-assessed progression-free survival 2.Overall survival
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Objective response 2.Duration of response 3.Clinically-meaningful improvement in abdominal pain or bloating using scales of the EORTC QLQ-OV28 for patients in the neoadjuvant group 4.Clinically-meaningful improvement, remaining stable or deterioration in function and HRQoL using scales of the EORTC QLQ-C30 for patients in the neoadjuvant group and the primary surgery group
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 108 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
China |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Korea, Republic of |
Norway |
Poland |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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When the approximate preplanned numbers of deaths among the PD-L1-positive patients and the intent-to-treat(ITT) population have been observed. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |