Double-blinded trial of platinum-based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal or peritoneal cancer.
- Conditions
- Recurrent ovarian, tubal or peritoneal cancerMedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000366-11-IT
- Lead Sponsor
- Grupo Español de Investigación en Cáncer de Ovario (GEICO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 414
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 3 months prior to randomization) sent to HistoGeneXcentral laboratory as a formalin-fixed, paraffin-embedded (FFPE) sample for PD-L1 status determination for randomization. The inclusion of patients with non informative tissue PD-L1 status will be capped to 10% of the whole study population. In case formalin fixed paraffin embedded (FFPE) blocks are not available at least 5 unstained FFPE slides. Two additional tumour samples are needed: Archival tumor sample must be available for exploratory PD-L1 testing in archival tissue and archival or fresh de novo” tissue sample for biomarkers must also be available.
10. Performance status determined by ECOG score of 0-1
11. 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.
12. Negative Test Results for Hepatitis
13. Toxicities related to previous treatments must be recovered to < grade 2 (with the exception of alopecia)
14. Female participants must be postmenopausal (= 12 months of non-therapy-induced amenorrhoea; patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation) or surgically sterile (absence of ovaries and/or uterus, or who received therapeutic radiation to the pelvis) or otherwise have a negative serum pregnancy test within 7 days of the first study treatment and agree to abstain from heterosexual intercourse or use single or combined contraceptive methods that result in a failure rate of <1% per year during the whole treatment period of the study and for at least 180 days after the last dose of study treatment
15. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
16. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 124
F.1
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 chemotherapy drugs, anticancer therapy or anti-neoplastic hormonal therapy, or treatment 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 or family history of long QT syndrome
11. Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal
12. History or clinical suspicion of brain metastases or spinal cord compression.
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 treatment related complications
19. Pregnant or lactating women
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.
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 human immunodeficiency virus (HIV)
27. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
28. Administration of a live, attenuated vaccine or anticipation that it will be administered at any time during the treatment period of the study
29. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
30. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation or allergy to any of the other drugs included in the protocol or their solvents (including to Cremophor®)
31. Patient has received prior treatment with a PARP inhibitor in the recurrent setting. Patients that received PARP inhibitor as front line are eligible for the study. The duration of exposure to PARPi following front line therapy needs to be =18 months for BRCA mutated p
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method