Histological confirmed endometrial cancer. (FIGO 2009) stage 3C2 or stage 4 or relapsed after adjuvant therapy for stage 1-3 disease. MedDRA version: 21.0 Level: PT Classification code 10014741 Term: Endometrial cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts
Conditions
Interventions
Trade Name: Vargatef
Product Name: Nintedanib 100 mg capsules
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: B
Sponsors
Nordic Society of Gynaecological Oncology (NSGO) - CTU
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria A patient will be eligible for inclusion only if all of the following criteria are fulfilled: 1. Histological confirmed endometrial cancer. (FIGO 2009) a) Stage 3C 2 b) Stage 4 A & B c) First relapse. Relapsed patients may (or may not) have recieved adjuvant chemotherapy. In case a pateint has received adjuvan chemotherapy, the treatment-free intervall should be >6 months. Prior therapy 2. Patients may have undergone primary surgery. 3. Patients may have received adjuvant chemotherapy for stage 1 – 3. 4. Patients may have received vaginal brachytherapy 5. Patients may have received external beam radiotherapy. Patients who are to be enrolled for stage 3C2 diseases are allowed to receive external beam radiotherapy prior to trial entry. 6. Patients may have received hormonal treatment Disease status 7. Patients must have measurable disease or non-measurable disease on CT scan according to RECIST 1.1 outside irradiated field. For stage 3C2 disease patients without measureable or non-measureable disease are accepted. Other inclusion criteria: 8. Patients must give informed consent 9. ECOG performance status of 0 -1 10. Patients must have an adequate organ function o Hepatic function: total bilirubin within normal limits; ALT and AST = 1.5 x ULN in pts without liver metastasis. For Pts with liver metastasis: total bilirubin within normal limits, ALT or AST = 2.5 ULN o Coagulation parameters: International normalised ratio ( INR) 45 ml/min (calculated using Cockroft & Gault equation, Jellife equation or measured by EDTA clearance ) 11. Life expectancy of at least 12 weeks 12. Patients must be fit to receive combination chemotherapy 13. Patient’s age > 18 years 14. Patients with preserved reproductive capacity must have a negative pregnancy test (ß-HCG test in urine or serum) prior to commencing 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: Exclusion criteria A patient will not be eligible for inclusion if any of the following criteria are fulfilled: Target Disease Exceptions: 1. Sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers. Prohibited Treatments and/or Therapies 2. Concurrent cancer therapy 3. Previous Chemotherapy for stage 4 disease or for relapsed disease. 4. Previous treatment with anti-angiogenic/anti VEGF therapy including nintendanib. 5. Concurrent treatment with an investigational agent or participation in another clinical trial. 6. Treatment within 28 days prior to randomisation with any investigational drug, radio-therapy, 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 involve target lesions, and the reason for the radiotherapy does not reflect progressive disease. 7. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period. Other exclusion criteria 8. Relapse within six months after adjuvant chemotherapy (treatment-free interval NYHA II, serious cardiac arrhythmia, pericardial effusion) See Appendix
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To compare Progression free survival (PFS). Progression Free Survival (PFS) is de-fined as the time from randomization until disease progression or death by any cause. The progression events are defined by RECIST 1.1 criteria ;Secondary Objective: Secondary objectives: • Compare Progression free survival (PFS) in the sub-populations. • Progression-free survival after consecutive treatment (PFS2). • Compare Disease Specific Survival (DSS). Disease Specific Survival (DSS) is defined as the time from start of treatment until date of death from en-dometrial cancer. • TSST (Time to Second Subsequent Therapy) • TFST (Time to First Subsequent Therapy) • Overall Survival (OS). A patient’s overall survival is defined as the time from start of treatment until date of death from any cause. • Response Rate (RR). • Disease Control Rate (DCR = Complete Response, Partial Response or Stable Disease for at least 12 weeks). • Patient Related Outcomes (e.g. QoL). • Toxicity in the two treatment arms • Compliance and Exposure in the two treatment arms. ;Primary end point(s): Primary end-point To compare Progression Free Survival (PFS) of patients treated with chemotherapy plus nintedanib against chemotherapy plus placebo. Progression Free Survival (PFS) is defined as the time from randomization until disease progression or death by any cause. ;Timepoint(s) of evaluation of this end point: Analysis will be perform once 124 events are registered No interim analysis is planned | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end-points • Compare Progression free survival (PFS) in the sub-populations as de-scribed under stratification factors. • Progression-free survival after consecutive treatment (PFS2). PFS2 is de-fined along the same timelines as PFS but accounts for the time from ran-domization to progression or death by any cause on any subsequent line of anticancer therapy. • Compare Disease Specific Survival (DSS). Disease Specific Survival (DSS) is defined as the time from start of treatment until date of death from en-dometrial cancer. • TSST (Time to Second Subsequent Therapy) • TFST (Time to First Subsequent Therapy) • Overall Survival (OS). A patient’s overall survival is defined as the time from start of treatment until date of death from any cause. • Response Rate (RR). • Disease Control Rate (DCR = Complete Response, Partial Response or Stable Disease for at least 12 weeks). • Patient Related Outcomes (e.g. QoL). • Toxicity in the two treatment arms • Compliance and Exposure in the two treatment arms. ;Timepoint(s) of evaluation of this end point: only after the primary endpoint is mature | — |
Countries
Belgium, Denmark, Finland, France, Germany, Norway, Sweden
Contacts
Public ContactStudy Project Management
NSGO
Outcome results
None listed