E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and neck squamous cell carcinoma
Colorectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Head and neck cancer
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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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 | 17.0 |
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) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the MTD and/or RDE of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients as measured by the incidence of DLTs in Cycle 1. |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency and severity of AEs/SAEs and the frequency of dose interruptions and dose reductions in patients treated with the combination of INC280 and cetuximab.
2. To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Overall Response Rate and Progression Free Survival in patients treated with the combination of INC280 and cetuximab.
3. To assess additional clinical activity of the INC280 and cetuximab combination as measured by Overall Survival for patients in the expansion part of the study.
4. To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female aged ≥ 18 years
• Metastatic colorectal cancer or head and neck squamous cell carcinoma
• c-MET positive (defined by c-MET IHC intensity score +2 or +3 in ≥ 50% of tumor cells) and K/NRAS-WT status for mCRC patients only
• At least one previous line of treatment for the metastatic disease and the last treatment must have included cetuximab or panitumumab. Documentation of clinical benefit and subsequent progression on cetuximab or panitumumab treatment is required for patients in the expansion part
• Measurable disease as per RECIST v1.1
• ECOG performance status ≤ 2
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E.4 | Principal exclusion criteria |
• Prior treatment with c-MET/HGF or EGFR inhibitors (with the exception of the last treatment)
• History of severe reactions to cetuximab and/or panitumumab (except for G3 rash and G3 hypomagnesaemia)
• History of acute or chronic pancreatitis
• Active bleeding within 4 weeks prior to screening visit
• Symptomatic brain metastases
• Feeding tube dependence
• Not adequate hematologic, renal and hepatic function
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed during cycle 1 of treatment with INC280 and cetuximab |
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E.5.2 | Secondary end point(s) |
1) Safety: Frequency and severity of AEs/SAEs
Tolerability: Frequency of dose interruptions and dose reductions
2) ORR and PFS per response evaluation criteria in solid tumors (RECIST) v1.1
3) OS (only in Expansion part)
4) Plasma concentration versus time profiles and basic PK parameters of INC280 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Assessed from C1D1 until treatment discontinuation
2) Assessed every 8 weeks from C1D1 up to the end of study
3) Assessed every 12 weeks up to the end of study
4) Assessed during the first 4 cycles of treatment
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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 escalation of INC280 and cetuximab |
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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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
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 |
China |
France |
Germany |
Italy |
Netherlands |
Spain |
United States |
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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
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End of study will be upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab, or when the study is terminated early. See protocol section 4.3 for details. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |