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: 20.0Level: LLTClassification code 10033130Term: Ovarian cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000366-11-DE
- Lead Sponsor
- Grupo Español de Investigación en Cáncer de Ovario (GEICO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 90
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) 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:
-If the mandatory de novo biopsy is technically not possible or failed to produce enough representative tumor tissue, a FFPE sample from archival tissue may be acceptable after approval of the sponsor.
-Bone metastases, fine needle aspiration, brushing, cell pellet from pleural effusion, or ascites or lavage are not acceptable.
10. Two additional tumour samples are needed: Archival tumor sample for exploratory PD-L1 testing in archival tissue and archival or ”de novo” tissue sample for biomarkers.
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 < grade 2 (with the exception of alopecia)
15. Examples of contraceptive methods with a failure rate of <1% per year include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (in-travaginal, transdermal*), progestogen-only hormonal contraception associated with inhibition of ovulation (injectable, implantable*), intrauterine device (IUD), intrauterine hormone-releasing sys-tem (IUS), bilateral tubal occlusion/ligation, vasectomized partner, sexual abstinence.
*Due to a reasonable frequency of emesis and diarrhea under the planned therapy, oral contraceptives are not considered highly effective”
16. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
17. 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 76
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of s
1. Non-epithelial tumor of the ovary, fallopian tube or 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
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 within 7 days prior to Day 1 Cycle 1
6. Administration of other chemotherapy drugs, anticancer therapy or antineoplastic hormonal therapy, or treatment with other investigational agents or devices within 28 days prior to randomization, or within a time interval less than at least 5 half-lives of the investigational agent
7. Palliative radiotherapy within 6 weeks prior to randomization or patients who have not completely recovered (Grade = 2) from the effects of previous 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 hour period 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 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 within 2 weeks prior to Cycle 1 Day 1
24. History of autoimmune disease: 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 syndrome, Guillain-Barré syndrome, 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. HIV)
27. Signs or symptoms of infection within 4 weeks prior to Cycle 1 Day 1
28. Active tuberculosis
29. Administration of a live, attenuated vaccine
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 hamster ovary cells or to any component of t
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