E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with chemorefractory colorectal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 explore the comparative effectiveness of BIBF 1120 in terms of progression free survival (PFS) |
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E.2.2 | Secondary objectives of the trial |
1. Objective response 2. Overall survival 3. Duration of overall response 4. Incidence and intensity of adverse events graded according to CTC AE version 3 5. Explorative analysis of predictive biomarkers for BIBF 1120
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients receiving mFOLFOX6 for histologically proven colorectal adenocarcinoma having received one previous line of chemotherapy 1. Age > = 18 years 2. Histologically proven colorectal adenocarcinoma 3. Metastatic disease not suitable for curative intent resection 4. Measurable (> 1 cm) and evaluable disease (according to RECIST 1.1 criteria) 5. Only one prior palliative chemotherapy for metastatic CRC 6. Prior bevacizumab permitted 7. No prior TKIs, no prior palliative treatmen twith oxaliplatin 8. Previous adjuvant therapy with an oxaliplatin containing regimen is allowed if the end of adjuvant chemotherapy is > 12 months prior to inclusion into the trial 9. ECOG performance status 0 or 1 10. Adequate hepatic function, renal function, bone marrow function, and lab parameters 11. Life expectancy at least three months 12. Signed and dated written infromed consent prior to admission to the study |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to the trial drugs or their excipients. 2. Treatment with any investigational drug within 28 days of trial onset. 3. Prior treatment with more than one line of palliative standard chemotherapy for colorectal cancer, prior treatment with a tyrosine kinase inhibitor, prior palliative treatment with an oxaliplatin-containing regime. 4. History of other malignancies in the last 5 years, in particular those which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell skin cancer are generally eligible. 5. Serious concomitant disease, especially those that would limit compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial. 6. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period. 7. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure > NYHA II). 8. History of severe haemorrhagic or thrombotic events in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). Known inherited predisposition to bleeds or to thrombosis. 9. Patient with brain metastases that are symptomatic and/or require therapy. 10. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid ≤ 325mg per day) 11. History of major thrombotic or clinically relevant major bleeding event in the past 6 months 12. Current peripheral neuropathy ≥ CTCAE grade 2 except due to trauma 13. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy 14. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug 15. Active alcohol or drug abuse. 16. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception 17. Pregnancy or breast-feeding 18. Leptomeningeal disease 19. Radiographic evidence of cavitary or necrotic tumours 20. Centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels |
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E.5 End points |
E.5.1 | Primary end point(s) |
This trial is designed with the primary endpoint of progression free survival (PFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final anaysis will be conducted when 145 randomized patients have died or experienced progressive disease. This is expected to take approximately two years. |
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E.5.2 | Secondary end point(s) |
Secondary endpoint is objective response (either complete or partial). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The final anaysis will be conducted when 145 randomized patients have died or experienced progressive disease. |
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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 | Yes |
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 | Yes |
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.8.3 |
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 | 20 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |