clear cell endometrial cancer clear cell ovarian cancer
Conditions
Interventions
The standard chemotherapy of physician*s choice consists of 3 options for
ovarian- and 2 options for endometrial clear cell cancer patients. Patients on
the standard arm will receive up to a maximum
Sponsors
European Organisation for Research and Treatment of Cancer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients will be eligible for the study if the following criteria are met: 1. Progressive or recurrent ovarian peritoneal or fallopian tube clear cell carcinoma, or progressive or recurrent endometrial clear cell carcinoma. The primary diagnosis must be histologically confirmed and central pathological review of the presenting tumour or biopsy of relapsed disease must find at least 50% clear cell carcinoma with no serous differentiation. Progressive disease as defined by RECIST 1.1 2. Failure after >=1 prior platinum containing regimen which may have been given in the adjuvant setting. For patients with ovarian clear cell carcinoma, progression must have occurred within 6 calendar months of their last platinum dose. 3. ECOG Performance status of 3 months 5. Adequate hepatic, bone marrow coagulation and renal function a. Hepatic function: total bilirubin=1.5 x 109/L d. Platelets >= 100 x 109L e. Haemoglobin >= 9.0 g/dL f. Proteinuria =40ml/min. (calculated using the Wright, Cockroft & Gault equation or measured by EDTA clearance) 6. Female and > 18 years of age 7. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and local legislation. 8. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures.
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study in the following circumstances: 1. Prior treatment with Nintedanib or other angiogenesis inhibitor/VEGF targeted therapy, except for prior treatment with bevacizumab which is permitted. 2. Treatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not affect target lesions, and the reason for the radiotherapy does not reflect progressive disease. 3. Previous treatment with the chemotherapy regimen selected as the control arm by the investigator. (Prior therapy with paclitaxel given on a three weekly regimen is permitted for patients receiving weekly Paclitaxel. Prior treatment with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel. Prior weekly paclitaxel for relapsed disease is not permitted). 4. Other malignancy diagnosed within 5 years of enrolment except for: a. Non-melanomatous skin cancer (if adequately treated) b. Cervical carcinoma in situ (if adequately treated) c. Carcinoma in situ of the breast (if adequately treated) d. For patients with ovarian clear cell cancer, prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met: • Disease stage FIGO Stage 1a (tumour invades less than one half of myometrium) • Grade 1 or 2 5. Patients with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgement of the investigator, would make the patient inappropriate for entry into this study, including significant neurologic, psychiatric, infectious, hepatic, renal, or gastrointestinal diseases or laboratory abnormality. 6. Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other gastro-intestinal disorders or abnormalities, including difficulty swallowing, that would interfere with drug absorption. 7. Serious infections in particular if requiring systemic NiCCC ISRCTN50772895 Version 3, 29th March 2016 Page 7 of 88 antibiotic (antimicrobial, antifungal) or antiviral therapy, including known hepatitis B and/or C infection and HIVinfection. 8. Symptomatic CNS metastasis or leptomeningeal carcinomatosis 9. Known, uncontrolled hypersensitivity to the investigational drugs or their excipients. 10.Hypersensitivity to Nintedanib, peanut or soya, or to any of the excipients of Nintedanib. 11.Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomisation, congestive heart failure > NYHA III, severe peripheral vascular disease or clinically significant pericardial effusion. 12.History of major thromboembolic event, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation 13. Known inherited predisposition to bleeding or thrombosis. 14.History of a cerebral vascular accident, transient ischemic<b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is progression free survival (PFS). The study is designed to detect an improvement in median PFS from 3 months with standard chemotherapy to 5 months with Nintedanib with 90 power, 20% 1-sided level of statitical significance for clear cell ovarian cancer. Up to 30 clear cell endometrial cancer patients will be randomized, but there is no specific power calculation for these patients as this disease is extremely rare, even more so than clear cell ovarian cancer, and it was not considered feasible to conduct more than an exploratory study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are overall survival, response rates, disease control rate, toxicity and quality of life. | — |
Countries
Netherlands
Outcome results
None listed