E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
colorectal adenocarcinoma.
metastatic pancreatic adenocarcinoma
melanoma |
|
E.1.1.1 | Medical condition in easily understood language |
colorectal adenocarcinoma
pancreatic adenocarcinoma
melanoma |
|
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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
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 | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or
recommended Phase II doses (RP2Ds) by measuring incidence of dose
limiting toxicities
Phase II: Antitumor activity of MEK162 in combination with AMG 479 by
evaluating Objective Response Rate (ORR) in colorectal carcinoma and
melanoma and by evaluating Disease Control Rate (DCR) at week 10 in
pancreatic carcinoma |
|
E.2.2 | Secondary objectives of the trial |
1. Phase Ib and II: To evaluate the safety and tolerability of MEK162 and AMG 479 (ganitumab) in combination.
2. Phase Ib and II: To determine single and multiple dose PK profile of
MEK162 in combination with AMG 479.
3. Phase Ib: To assess preliminary anti-tumor activity of MEK162 and
AMG 479 (ganitumab) in combination
4. Phase II: To further assess the anti-tumor activity of MEK162 and AMG 479 (ganitumab) in all three Phase II populations |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients aged ≥ 18 years
• Patients with advanced solid tumors (CRC, melanoma) with
documented somatic KRAS or BRAFV600 mutations in tumor tissue.
Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
• Patients must have relapsed or progressed following standard
or patients for whom no standard anticancer therapy exists.
• Measurable disease as determined by RECIST v1.1. World Health
Organization (WHO) Performance Status (PS) ≤ 2.
• Adequate organ function
• Negative serum pregnancy test
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
• Prior therapy with MEK- or IGF-1R- inhibitor
• History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease
• Patients with known history of severe infusion reactions to monoclonal antibodies
• Patients with primary CNS tumor or CNS tumor involvement
• History of thromboembolic event requiring full-dose anticoagulation therapy
• Clinically significant cardiac disease
• History of another malignancy within 2 years
• Pregnant or nursing (lactating) women
Other protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: measuring incidence of dose limiting toxicities in cycle 1.
Phase II: Objective Response Rate (ORR) in colorectal carcinoma and melanoma and Disease Control Rate (DCR) at week 10 in pancreatic carcinoma |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase Ib: Approximately 6 months
Phase II: Approximately 24 months |
|
E.5.2 | Secondary end point(s) |
1. Phase Ib and II: Evaluating the adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity
2. Phase Ib and II: Measuring time vs. plasma concentrations and basic PK parameters of MEK162
3. Phase Ib: Evaluating the Overall Response Rate (ORR), Duration of Response (DOR) and Progression Free Survival (PFS)
4. Phase II:Evaluating the Duration of Response (DOR), Progression Free Survival (PFS), and Overall Survival (OS) in all phase II patients and by evaluating Disease Control Rate (DCR) for colorectal carcinoma and melanoma; Overall Response Rate (ORR) for pancreatic carcinoma patients |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Phase Ib: Approximately 6 months ;Phase II: Approximately 24 months
2. Phase Ib: Approximately 6 months ;Phase II: Approximately 24 months
3. Approximately 6 months
4. Approximately 24 months |
|
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 |
Italy |
Australia |
Germany |
Spain |
United Kingdom |
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 AMG 479 (ganitumab). |
|
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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |