| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced or recurrent cervical carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced or recurrent cervical carcinoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008229 |
| E.1.2 | Term | Cervical cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| - To evaluate the progression free survival |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the toxicity and safety profile
- To evaluate the response rate and overall survival
- To explore the effect on patient reported health status as measured by QOL-cx24 and EORTCQLQ-C30 questionnaires |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. Prior treatment with angiogenisis inhibitors is allowed
4. Up to one prior line of chemotherapy for metastatic cervical cancer is allowed.
•Treatment of primary disease with concomitant cisplatinum chemotherapy during radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease
•Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery is allowed and does not count as a line of chemotherapy for metastatic disease.
o Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
o Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
5. Life expectancy at least (3 months)
6. ECOG performance status score of 0 or 1
7. At least one measurable lesion according to RECIST 1.1 criteria.
8. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation
|
|
| E.4 | Principal exclusion criteria |
9. Known hypersensitivity to the trial drugs or to their excipients (including peanuts and soya)
10. Brain or leptomeningeal metastases.
11. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
12. Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract.
13. Radiographic evidence of cavitary or necrotic tumours
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 with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or antiplatelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day)
16. Major injuries within the past 4 weeks 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 inherited predisposition to bleeding or thrombosis
19. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 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. Significant abnormal renal, liver or bone marrow function
22. Other malignancies within the past 3 years.
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 (based on medical file, only for Italy a mandatory screening test for HIV should be performed for all patients who did not have this test within the last 3 months before the study treatment start).
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 of child-bearing potential 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 or sexual abstinence for participating females) during the trial and for at least three months after end of active therapy.
28. Pregnancy or breast feeding, female patients must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment, if applicable.
29. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.
30. Active alcohol or drug abuse. |
|
| E.5 End points |
| E.5.1 | 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.
The primary analyses will take an intent-to-treat approach of all randomised patients that will be treated with the study drug (BIBF/Placebo).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The analysis is event driven and will be performed once 87 events have occured
Estimated: 1.5 years after last patient in |
|
| E.5.2 | Secondary end point(s) |
To evaluate toxicity and safety profile
To evaluate the response rate and overall survival
To explore the effect on patient reported health status as measured by QOL-Cx 24/QOQ-C30 questionnaires |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The analysis is driven by survival information
Estimated: at latest 5 years after last patient in |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The clinical trial will be considered completed as soon as the last patient has died or was lost to follow-up or at the time of the final analysis at the latest.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
Print
