| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic colorectal cancer |
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| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| Overall response rate in the study population; objective response rate in the KRAS wild type subgroup; and disease control rate in the KRAS mutated subgroup. |
|
| E.2.2 | Secondary objectives of the trial |
| Progression-free survival, overall survival; safety of BIBW 2992; explorative analyses of biomarkers. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven colorectal adenocarcinoma.
2. Metastatic disease, not amenable to potentially curative treatment.
3. Tumour sample available for KRAS mutation testing and other biomarker analyses.
If the patient previously had their tumour tested for KRAS mutation in another study or as part of routine clinical management, there will be no need for re-testing provided the lab that performed the test has the appropriate qualifications and certifications. A copy of this test result must be available for determination of
patient’s eligibility for study entry. However, there must be adequate tumour sample
remaining for analyses of other biomarkers as specified in Section 5.6.
4. Patient must have completed their previous line of treatment (i.e. last day of the last cycle) within the past 12 weeks prior to informed consent. Patients must have progressed on or after this previous line of treatment (with the exception of patients with peripheral neuropathy as per Inclusion Criteria #5)
5. Patient must have failed both oxaliplatin- and irinotecan-based regimens, whether these were given in the adjuvant or palliative setting. Patients with persistent peripheral neuropathy secondary to prior oxaliplatin who are deemed not suitable for further oxaliplatin but whose disease has not progressed on the oxaliplatin-based regimen, are eligible for this study.
6. At least one measurable lesion according to RECIST 1.1 criteria.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 .
8. Age ≥18 years.
9. Life expectancy of at least three (3) months.
10. Complete recovery of toxicities from previous lines of anticancer therapy. An exception is peripheral neuropathy – this must have improved to ≤ grade 2 to be eligible for this study.
11. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and local legislation.
|
|
| E.4 | Principal exclusion criteria |
1. Prior treatment with EGFR targeting small molecules or antibodies.
2. Radiotherapy, surgery or any major procedures (other than biopsy) within 4 weeks prior to start of study treatment. Treatment with palliative radiotherapy (short course, to non target lesions) is allowed. Any experimental anti-cancer treatment, chemotherapy, immunotherapy, hormone treatment (with the exception of megestrol acetate) must be ceased at least 4 weeks prior to start of study treatment.
3. Biological therapy (including Bevacizumab or any other anti-angiogenic agents) during the trial is not permitted. Prior treatment with these agents are allowed but they must be ceased at least 4 weeks prior to start of study treatment.
4. Planned major surgical procedures during the trial period.
5. Patients with untreated or symptomatic brain metastases. Patients with treated or
asymptomatic brain metastases are eligible provided there has been no change in their brain disease status for at least 4 weeks, no history of cerebral oedema or bleeding in the past 4 weeks prior to start of study treatment. Anti-epileptic therapy is allowed provided there has not been any change in the dose of the anti-epileptic drug in the last 4 weeks prior to start of study treatment.
6. Any other current malignancy or malignancy diagnosed or relapsed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
7. Known pre-existing interstitial lung disease.
8. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE grade ≥2 diarrhoea of any aetiology.
9. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable
angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to
start of study treatment.
10. Cardiac left ventricular function with resting ejection fraction of less than 50%.
11. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
12. Absolute neutrophil count (ANC) < 1500 / mm3.
13. Platelet count < 100,000 / mm3.
14. Creatinine clearance < 60 ml / min (using Cr51-EDTA or Cockcroft-Gault formula)
15. Bilirubin > 1.5 times upper limit of normal.
16. Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is objective response (complete response, partial response) according to RECIST 1.1 . This includes overall response rate, response rate in the KRAS wild-type subgroup and disease control rate (complete response, partial response, stable disease) in the KRAS mutated subgroup.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 6 months after start of treatment |
|
| E.5.2 | Secondary end point(s) |
| Progression-free survival, Overall survival, safety of BIBW 2992, explorative analysis of biomarkers, pharmacokinetic analysis |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 6 months after start of study treatment |
|
| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 10 |
| 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 | Information not present in EudraCT |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
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