Squamous Cell Carcinoma of Head and Neck (SCCHN)Phase 1NCT02205398
Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy
A Phase 1 study testing INC280 and cetuximab in people with Squamous Cell Carcinoma of Head and Neck (SCCHN) and Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
Trial summary
This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck (SCCHN), Metastatic Colorectal Cancer
- What is being tested?
- INC280 and cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 15 sitesin 7 countries
- Study dates
- 28 Jul 2014to 20 Jan 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 in ≥ 50% of tumor cells and MET gene copy number ≥ 5 by FISH or IHC intensity score +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 as the most recent line of treatment is required for patients in the expansion part
- Measurable disease as per RECIST v1.1
- ECOG performance status ≤ 2
Who cannot join
- Prior treatment with c-MET/HGF inhibitors
- 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
Trial locations and contacts
15 sites in 7 countries.
15 sites in 7 countries
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Valencia, Valencia, 46010
United States3 sites
Massachusetts General Hospital Head & Neck
Boston, Massachusetts, 02114
Memorial Sloan Kettering MSKCC NY
New York, New York, 10017
University of Utah / Huntsman Cancer Institute Onc Dept
Salt Lake City, Utah, 84103
France2 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Toulouse, 31059
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Würzburg, 97080
Italy2 sites
Novartis Investigative Site
Ancona, AN, 60126
Novartis Investigative Site
Milan, MI, 20162
About this study
Official title: A Phase Ib, Open-label, Multicenter, Dose Escalation and Expansion Study, to Evaluate the Safety, Pharmacokinetics and Activity of INC280 in Combination With Cetuximab in c-MET Positive CRC and HNSCC Patients Who Have Progressed After Anti-EGFR Monoclonal Antibody Therapy.
This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who progressed on cetuximab or panitumumab treatment were to be enrolled in two expansion groups to further assess the anti-tumor activity and the safety and tolerability of the combination of INC280 and cetuximab. Patients were to receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no scheduled break between cycles.
The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.
- Being tested
- INC280, cetuximab
- Keywords
- INC280, c-MET inhibitor, cetuximab, metastatic colorectal cancer, head and neck, squamous cell carcinoma, resistance to cetuximab/panitumumab, SCCHN,, cancer, oral and nasal cavity, paranasal sinuses, pharynx, larynx, parotid glands, lympth nodes of neck, mucosal lining, epithelium, colon, large intestine, rectal cancer
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Carcinoma, Squamous Cell, Neoplasms, Laryngeal Diseases, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280Drug
cetuximabDrug
| Study group | Role | What they receive |
|---|---|---|
| c-MET positive mCRC and HNSCC | Experimental | c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients Receives: Drug: INC280; Drug: cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities (DLTs)
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. A treatment cycle was defined as 28 days with no scheduled break between cycles.
Measured: during Cycle 1 and up to 4 weeks from the time of study treatment start
Secondary outcomes (7)
Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of AEs/SAEs in patients treated with the combination of INC280 and cetuximab
Measured: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
Overall Response Rate
To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Overall Response Rate in patients treated with the combination of INC280 and cetuximab. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. A treatment cycle was defined as 28 days with no scheduled break between cycles.
Measured: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
Overall Survival
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. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.
Measured: Every 12 weeks until the end of study for up to 3 years
Time versus plasma concentration profiles and basic PK parameters of INC280
To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280. A treatment cycle was defined as 28 days with no scheduled break between cycles.
Measured: during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by severity of AEs/SAEs in patients treated with the combination of INC280 and cetuximab
Measured: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Frequency of dose treatment interruptions and reductions
To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of dose interruptions and dose reductions in patients treated with the combination of INC280 and cetuximab
Measured: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Progression Free Survival
To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Progression Free Survival in patients treated with the combination of INC280 and cetuximab.The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.
Measured: Every 8 weeks from C1D1 until the end of study for up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2014 (estimated)
- Study start28 Jul 2014
- Primary completion20 Jan 2017
- Study completion20 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of Head and Neck (SCCHN)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02205398
- Sponsor's protocol ID
- CINC280X2104
- Other IDs
- 2014-000579-20, 2014
- Status last verified
- Jan 2019
- First submitted
- 25 Jul 2014
- Last updated
- 22 Jan 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Delord JP, Argiles G, Fayette J, Wirth L, Kasper S, Siena S, Mesia R, Berardi R, Cervantes A, Dekervel J, Zhao S, Sun Y, Hao HX, Tiedt R, Vicente S, Myers A, Siu LL. A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer who had progressed following anti-EGFR monoclonal antibody treatment. Invest New Drugs. 2020 Dec;38(6):1774-1783. doi: 10.1007/s10637-020-00928-z. Epub 2020 May 14.
PubMed 32410080
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label, Multicenter, Dose Escalation and Expansion Study, to Evaluate the Safety, Pharmacokinetics and Activity of INC280 in Combination With Cetuximab in c-MET Positive CRC and HNSCC Patients Who Have Progressed After Anti-EGFR Monoclonal Antibody Therapy.
- ClinicalTrials.gov ID
- NCT02205398
- Acronym / sponsor ID
- CINC280X2104
- Keywords
- INC280, c-MET inhibitor, cetuximab, metastatic colorectal cancer, head and neck, squamous cell carcinoma, resistance to cetuximab/panitumumab, SCCHN,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2014 (actual)
- Primary completion
- 20 Jan 2017 (actual)
- Study completion
- 20 Jan 2017 (actual)
- First posted
- 31 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who progressed on cetuximab or panitumumab treatment were to be enrolled in two expansion groups to further assess the anti-tumor activity and the safety and tolerability of the combination of INC280 and cetuximab. Patients were to receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no scheduled break between cycles.
The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| c-MET positive mCRC and HNSCC | Experimental | Drug: INC280, Drug: cetuximabc-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 in ≥ 50% of tumor cells and MET gene copy number ≥ 5 by FISH or IHC intensity score +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 as the most recent line of treatment is required for patients in the expansion part
- Measurable disease as per RECIST v1.1
Key exclusion criteria (7 listed)
- Prior treatment with c-MET/HGF inhibitors
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INC280 | Drug | c-MET positive mCRC and HNSCC |
| cetuximab | Drug | c-MET positive mCRC and HNSCC |
Primary outcome
Incidence of Dose Limiting Toxicities (DLTs)
Time frame: during Cycle 1 and up to 4 weeks from the time of study treatment start
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. A treatment cycle was defined as 28 days with no scheduled break between cycles.
7 secondary outcomes
Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Time frame: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
Overall Response Rate
Time frame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
Overall Survival
Time frame: Every 12 weeks until the end of study for up to 3 years
Time versus plasma concentration profiles and basic PK parameters of INC280
Time frame: during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Frequency of dose treatment interruptions and reductions
Time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Progression Free Survival
Time frame: Every 8 weeks from C1D1 until the end of study for up to 3 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Derived from this study: PubMed 32410080Delord JP, Argiles G, Fayette J, Wirth L, Kasper S, Siena S, Mesia R, Berardi R, Cervantes A, Dekervel J, Zhao S, Sun Y, Hao HX, Tiedt R, Vicente S, Myers A, Siu LL. A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer who had progressed following anti-EGFR monoclonal antibody treatment. Invest New Drugs. 2020 Dec;38(6):1774-1783. doi: 10.1007/s10637-020-00928-z. Epub 2020 May 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INC280 and cetuximab in people with Squamous Cell Carcinoma of Head and Neck (SCCHN) and Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain, United States, France, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting Toxicities (DLTs) (time frame: during Cycle 1 and up to 4 weeks from the time of study treatment start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02205398, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.