E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mutant RAS or wild-type (WT) RAS metastatic colorectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Mutant RAS or wild-type (WT) RAS metastatic colorectal cancer |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10010023 |
E.1.2 | Term | Colorectal neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010030 |
E.1.2 | Term | Colorectal cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
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 | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase Ib: To estimate the MTD and/or RP2D of MEK162 in combination with panitumumab
Phase II: To assess clinical efficacy of the MEK162 and panitumumab combination |
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E.2.2 | Secondary objectives of the trial |
Phase Ib and Phase II
To characterize the safety and tolerability of the MEK162 and panitumumab combination
Phase Ib only
To assess preliminary anti-tumor activity of the MEK162 and panitumumab combination
Phase II only
To assess additional anti-tumor activity of the MEK162 and panitumumab combination
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years
2. Histological or cytological confirmation of mCRC
3. For the dose escalation (Phase Ib): Progression on or following standard therapy or for whom no standard therapy exists. See protocol for complete details
4. Phase Ib and Phase II: Written documentation of WT RAS or somatic mutation in exon 2 (codons 12/13), 3 (codons 59/61) or 4 (codons 117/146) in either KRAS or NRAS in medical history.
5. Evidence of measurable disease, as determined by RECIST v1.1.
6. Life expectancy ≥ 3 months.
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1.Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors. For arms 2 and 3: EGFR tyrosine kinase inhibitor therapy.
2.Previous treatment with MEK-inhibitors - certain exceptions. See protocol
3.Patients with known history of severe infusion reactions to monoclonal antibodies.
4.Known hypersensitivity and/or contraindication to any of the study medications or their excipients
5.Symptomatic or untreated leptomeningeal disease.
6.Symptomatic brain metastasis.
7.History or current evidence of retinal disease or ophthalmopathy
8.History of keratitis or ulcerative keratitis.
9.Known acute or chronic pancreatitis.
10.Clinically significant cardiac disease - see ptotocol
12.Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral MEK162
13.Previous or concurrent malignancy - with exceptions - see protocol
14.History of thromboembolic or cerebrovascular events within the last 6 months
15.Patients who have received radiation therapy , chemotherapy, biological therapy within ≤ 4 weeks or who have been treated with continuous or intermittent small molecule therapeutics or investigational agents within 5 half-lives of the agent - See protocol
16.Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery.
17.Known human immunodeficiency virus (HIV) infection.
18.Pregnant or nursing (lactating) women
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Phase II: Overall response rate (ORR) as per RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DLTs- Approximately 3-6 months
ORR- Approximately 12 months |
|
E.5.2 | Secondary end point(s) |
Phase Ib: ORR, Progression-free survival, (PFS), duration of response (DOR), disease control rate
(DCR) as per RECIST v1.1
Phase II: PFS, DOR, DCR as per RECIST v1.1 and OS
Phase Ib and Phase II: Frequency and severity of Adverse Events (AEs), SAEs, changes in laboratory
values, vital signs, and electrocardiograms
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|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 12-18 months |
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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 | No |
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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose-finding, Dose-escalation |
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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 | No |
E.8.1.1 | Randomised | No |
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) | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United States |
|
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
|
End of study will be upon completion of the follow-up period of the last
patient treated with the combination of MEK162 and panitumumab |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |