Study comparing 3-weekly carboplatin + paclitaxel with or without concomitant and maintenance nintedanib (NINTEDANIB) in advanced or recurrent cervical carcinoma.

• Conditions: Advanced or recurrent cervical carcinoma; MedDRA version: 17.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004076-19-ES
• Lead Sponsor: Z Leuven / Belgian Gynaecological Oncology Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-24
• Last Update Posted: 2 February 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 120

Inclusion Criteria

1. Women age > 18
2. Histologically or cytologically confirmed advanced (FIGO stage IVB), or recurrent/persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix will be eligible.
3. No prior chemotherapy for recurrent cervical cancer.
?Prior concomitant cisplatinum chemotherapy during radiotherapy is allowed (except if recurrence is within 6 months after the end of the platinum containing chemotherapy).
?Cases primarily treated with neoadjuvant chemotherapy before radical local surgery are eligible at the time of first recurrence. (except if recurrence is within 6 months after the end of the platinum containing chemotherapy).
?Cases primarily treated with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy are eligible at the time of first recurrence (except if recurrence is within 6 months after the end of the platinum containing chemotherapy).
?Cases primarily treated with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy are eligible at the time of first recurrence (except if recurrence is within 6 months after the end of the platinum containing chemotherapy).
4. Life expectancy at least (3 months)
5. ECOG performance status score of 0 or 1
6. At least one measurable lesion according to RECIST 1.1 criteria.
7. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

8. Prior chemotherapy except platin-based concomitant chemotherapy during radiotherapy
9. Prior treatment with nintedanib or any other VEGFR inhibitor
10. Known hypersensitivity to the trial drugs or to their excipients
11. Brain or leptomeningeal metastases
12. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
13. Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract.
14. Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
15. Therapeutic anticoagulation is not allowed, unless the patient is on stable anti-coagulation.
16. Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
17. History of clinically significant haemorrhagic or thromboembolic event in the past 6 months
18. Known inheritated predisposition to bleeding or thrombosis
19. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina within the past 6 months, history of infarction within the past 6 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
20. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
21. Abnormal renal, liver or bone marrow function defined as:
? Proteinuria CTCAE grade 2 or greater
? Creatinin > 2 ULN or GFR < 30 ml/min
? Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN in pts without liver metastasis. For Pts with liver metastases: total bilirubin outside of normal limits, ALT or AST > 2.5 ULN
? Coagulation parameters: International normalised ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
? Absolute neutrophil count ( ANC) < 1500/µl, platelets < 100000/µl, Haemoglobin < 9.0 g/dl
22. Other malignancies within the past 3 years or other malignancy with recurrence the past 3 years or with high risk of recurrence in the first year. In exception to this rule, the following malignancies may be included: non-melanomatous skin cancer (if adequately treated) , any premalignant (e.g. in situ) carcinoma, or basocellular carcinoma.
23. Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
24. Active or chronic hepatitis C and/or B infection or known HIV infection
25. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
26. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
27. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females,) during the trial and for at least three months after end of active therapy
28. Pregnancy or breast feed

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate the progression free survival;Secondary Objective: - To evaluate the toxicity and safety profile<br>- To evaluate the response rate and overall survival<br>- To explore the effect on patient reported health status as measured by QOL-cx24 and EORTCQLQ-C30 questionnaires;Primary end point(s): The primary objective of this trial is to determine whether BIBF in combination with standard chemotherapy significantly prolongs progression-free survival in comparison with placebo combined with standard chemotherapy. <br>The primary analyses will take an intent-to-treat approach of all randomised patients that will be treated with the study drug (BIBF/Placebo).;Timepoint(s) of evaluation of this end point: The analysis is event driven and will be performed once 87 events have occured<br>Estimated: 1.5 years after last patient in

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To evaluate toxicity and safety profile<br>To evaluate the response rate and overall survival <br>To explore the effect on patient reported health status as measured by QOL-Cx 24/QOQ-C30 questionnaires;Timepoint(s) of evaluation of this end point: The analysis is driven by survival information<br>Estimated: at latest 5 years after last patient in