Oesophageal AdenocarcinomaPhase 2METIMGASTNCT05135845
Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
A Phase 2 study testing Capmatinib and Spartalizumab in people with Oesophageal Adenocarcinoma and Gastric Adenocarcinoma, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
Trial summary
Immunotherapy with anti-PD1 antibodies provides encouraging results on a subset of patients. Capmatinib, a MET inhibitor, has shown an imunomodulatory effect and a synergy with spartalizumab a PD-1 inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oesophageal Adenocarcinoma, Gastric Adenocarcinoma
- What is being tested?
- Capmatinib and Spartalizumab
- How many people
- 90 participants
- Where
- 7 sitesFrance
- Study dates
- 22 Mar 2022to Oct 2025
- Phase
- Phase 2
- 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
- Histologically or cytologically documented locally advanced or metastatic oesogastric adenocarcinoma.
- Unresectable tumor.
- Patients must have received at least one prior systemic chemotherapy based on platinium salt and fluoropyrimidine with documented progression during chemotherapy.
- Patients must have received trastuzumab in case of HER2 positive tumor (HER2 +++ or HER2++ and FISH or SISH+)
- Determination of tumor MET amplification by FISH available
- ECOG Performance Status ≤ 1.
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- Measurable tumoral disease according to RECIST 1.1 criteria.
- Patients must be willing and able to swallow and retain oral medication.
- Age ≥18 years.
- Women of childbearing potential and males who are sexually active must agree to follow instructions for method(s) of contraception for the duration of study treatments with Capmatinib and Spartalizumab until 7 days after the last dose of Capmatinib and 150 days after the last dose of Spartalizumab
- Consent to participate in the trial after information
- Affiliated to a social security system
Who cannot join
- Previous treatment with immunotherapy or MET inhibitor
- Impossibility to take oral medication
- Persistent toxicities related to prior treatment of grade greater than 1
- Presence or history of another malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Use of any live vaccines within 4 weeks of initiation of study treatment.
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
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- History or current interstitial lung disease or non-infectious pneumonitis
- Active autoimmune disease or a documented history of autoimmune disease (Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted).
- Allogenic bone marrow or solid organ transplant
- Uncontrolled active infection
- Human Immunodeficiency Virus (HIV) infection
- Untreated active Hepatitis B infection (HBsAg positive) (Patients with active hepatitis B (HBsAg positive) may be enrolled provided viral load (HBV DNA) at screening is <100 UI/mL. Patients may receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents before the initiation of study treatment to suppress viral replication).
- Untreated active hepatitis C (HCV RNA positive) (patients that achieved a sustained virological response after antiviral treatment and show absence of detectable HCV RNA ≥6 months after cessation of antiviral treatment are eligible)
- Untreated or symptomatic central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥2 weeks
- Clinically significant, uncontrolled heart diseases
- Recent acute coronary syndrome or unstable ischemic heart disease
- Congestive heart failure ≥ Class III or IV as defined by New York Heart Association
- Long QT syndrome (> 480 ms in women and 470 ms in men), family history of idiopathic sudden death or congenital long QT syndrome.
- Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥150 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
- Surgery less than 4 weeks
- Radiotherapy less than 2 weeks
- Pregnancy or breastfeeding or women of child-bearing potential, unless they are using highly effective methods of contraception.
- Sexually active males unless they use a condom during intercourse while taking capmatinib and for 7 days after stopping treatment and should not father a child in this period.
- Participants receiving treatment with strong inducers of CYP3A and could not be discontinued ≥ 1 week prior to the start of treatment.
- Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment.
- Patient having out of range laboratory values defined as:
- Total bilirubin >2 mg/dL, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN
- Alanine aminotransferase (ALT) > 3 x ULN
- Aspartate aminotransferase (AST) > 3 x ULN
- Coagulation: Prothrombin Time (PT) >4 seconds more than the ULN or International Normalized Ratio (INR) >1.7
- Absolute neutrophil count (ANC) <1.5 x 109/L
- Platelet count <75 x 109/L
- Hemoglobin <9 g/dL
- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) <45 mL/min
- Serum lipase >1 ULN
- Cardiac troponin I (cTnI) elevation >2 x ULN
- Potassium, Magnesium, Phosphorus, total Calcium (corrected for serum albumin) outside of normal limits (patients may be enrolled if corrected to within normal limits with supplements during screening)
- Patients under legal protection
- Participation to another interventional study with treatment
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
Hôpital Jean Minjoz
Besançon, 25030
Centre François Leclerc
Dijon
Centre Léon Bérard
Lyon, 69008
AP-HP Hôpital Saint Louis
Paris, 75010
Hôpital Haut Lévêque
Pessac, 33604
Institut Universitaire du Cancer
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94805
About this study
Official title: Phase II Trial to Evaluate the Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
Immunotherapy with anti-PD1 antibodies provides encouraging results on a subset of patients. Capmatinib, a MET inhibitor, has shown an imunomodulatory effect and a synergy with spartalizumab a PD-1 inhibitor. The purpose of this phase II trial is to evaluate the efficacy and safety of the combination of capmatinib + spartalizumab in adult patients with advanced oesogastric adenocarcinoma.
- Conditions
- Oesophageal Adenocarcinoma, Gastric Adenocarcinoma
- Being tested
- Capmatinib, Spartalizumab
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapmatinibDrug
Also called INC280
Capmatinib 400mg BID for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity
SpartalizumabDrug
Also called PDR001
Spartalizumab 300mg Q3W for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor response
Overall response rate defined as the proportion of patients with at least one objective tumour response (complete or partial) according to response evaluation criteria in solid tumours (RECIST) v1.1 within 6 months.
Measured: 6 months
Secondary outcomes (7)
Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration
Presence of at least one of (composite endpoint):
- Adverse event (AE) grade >3 (NCI-CTCAE v5), at least possibly related to the treatment or unrelated to disease, progression, intercurrent illness, concomitant medications
- Non-hematological AE grade ≥3
- Recurring grade 2 pneumonitis, Myocarditis grade ≥2
- Autoimmune hemolytic anemia, hemolytic uremic syndrome, acquired hemophilia grade ≥3
- Guillain-Barre, severe peripheral or autonomic neuropathy, transverse myelitis, encephalitis, aseptic meningitis
- Laboratory abnormality grade ≥3 for >7days (except nephritis grade 3-4, combined elevations of aspartate or alanine transaminase and total bilirubin, hyperglycemia, serum electrolytes/enzymes changes without clinical impact)
- Febrile neutropenia, documented infection with absolute neutrophil count<10^9/L, grade 3 neutropenia >7days, grade 4 neutropenia or thrombocytopenia, or bleeding with platelet transfusion
- AE with discontinuation >21days
- Significant drug-related AE
Measured: Day 42
Proportion of unacceptable toxicity of the regimen during the whole treatment course
Presence of at least one of (composite endpoint):
- Adverse event (AE) grade >3 (NCI-CTCAE v5), at least possibly related to the treatment or unrelated to disease, progression, intercurrent illness, concomitant medications
- Non-hematological AE grade ≥3
- Recurring grade 2 pneumonitis, Myocarditis grade ≥2
- Autoimmune hemolytic anemia, hemolytic uremic syndrome, acquired hemophilia grade ≥3
- Guillain-Barre, severe peripheral or autonomic neuropathy, transverse myelitis, encephalitis, aseptic meningitis
- Laboratory abnormality grade ≥3 for >7days (except nephritis grade 3-4, combined elevations of aspartate or alanine transaminase and total bilirubin, hyperglycemia, serum electrolytes/enzymes changes without clinical impact)
- Febrile neutropenia, documented infection with absolute neutrophil count<10^9/L, grade 3 neutropenia >7days, grade 4 neutropenia or thrombocytopenia, or bleeding with platelet transfusion
- AE with discontinuation >21days
- Significant drug-related AE
Measured: 12 months or treatment discontinuation
Proportion of patients with adverse events during the whole treatment course
All adverse events during the whole treatment course
Measured: 12 months or treatment discontinuation
Duration of overall response
Time between the first occurrence of tumor objective response, partial or complete (RECIST 1.1) and the first radiological progression, with response assessment every 9 weeks, up to 24 months
Measured: 24 months
Time to response
Time between inclusion and the first occurrence of tumor objective response (complete or partial, according to RECIST 1.1) or the end of the study, with response assessment every 9 weeks, up to 24 months
Measured: 24 months
Progression-free survival
Time between inclusion and the date of the first radiological progression (according to RECIST 1.1), death (any cause), or last follow-up (maximum=24 months), whichever occurs first.
Measured: 24 months
Overall survival
Time between inclusion and death (any cause) or last follow-up (maximum=24 months), whichever occurs first
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study start22 Mar 2022
- Primary completionApr 2023 (estimated)
- Study completionOct 2025 (estimated)
Why it stopped: Sponsor decision up DSMB advice due to unfavorable toxicity profile
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oesophageal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Multicenter single-arm adaptive phase II trial with 2 cohorts according to MET amplification level : * Cohort 1: tumor without MET amplification (\< 6 copies); * Cohort 2: tumor with MET amplification (≥6 copies).
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05135845
- Sponsor's protocol ID
- APHP201152
- Acronym
- METIMGAST
- Status last verified
- Jan 2023
- First submitted
- 28 Oct 2021
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial to Evaluate the Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
- ClinicalTrials.gov ID
- NCT05135845
- Acronym / sponsor ID
- METIMGAST / APHP201152
- Conditions
- Oesophageal Adenocarcinoma, Gastric Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Sponsor decision up DSMB advice due to unfavorable toxicity profile
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 22 Mar 2022 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 26 Nov 2021 (actual)
- 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.
Immunotherapy with anti-PD1 antibodies provides encouraging results on a subset of patients. Capmatinib, a MET inhibitor, has shown an imunomodulatory effect and a synergy with spartalizumab a PD-1 inhibitor. The purpose of this phase II trial is to evaluate the efficacy and safety of the combination of capmatinib + spartalizumab in adult patients with advanced oesogastric adenocarcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Model description
- Multicenter single-arm adaptive phase II trial with 2 cohorts according to MET amplification level : * Cohort 1: tumor without MET amplification (< 6 copies); * Cohort 2: tumor with MET amplification (≥6 copies).
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically or cytologically documented locally advanced or metastatic oesogastric adenocarcinoma.
- Unresectable tumor.
- Patients must have received at least one prior systemic chemotherapy based on platinium salt and fluoropyrimidine with documented progression during chemotherapy.
- Patients must have received trastuzumab in case of HER2 positive tumor (HER2 +++ or HER2++ and FISH or SISH+)
- Determination of tumor MET amplification by FISH available
Key exclusion criteria (39 listed)
- Previous treatment with immunotherapy or MET inhibitor
- Impossibility to take oral medication
- Persistent toxicities related to prior treatment of grade greater than 1
- Presence or history of another malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Use of any live vaccines within 4 weeks of initiation of study treatment.
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 |
|---|---|---|
| CapmatinibAlso: INC280Capmatinib 400mg BID for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity | Drug | – |
| SpartalizumabAlso: PDR001Spartalizumab 300mg Q3W for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity | Drug | – |
Primary outcome
Tumor response
Time frame: 6 months
Overall response rate defined as the proportion of patients with at least one objective tumour response (complete or partial) according to response evaluation criteria in solid tumours (RECIST) v1.1 within 6 months.
7 secondary outcomes
Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration
Time frame: Day 42
Proportion of unacceptable toxicity of the regimen during the whole treatment course
Time frame: 12 months or treatment discontinuation
Proportion of patients with adverse events during the whole treatment course
Time frame: 12 months or treatment discontinuation
Duration of overall response
Time frame: 24 months
Time to response
Time frame: 24 months
Progression-free survival
Time frame: 24 months
Overall survival
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2023.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capmatinib and Spartalizumab in people with Oesophageal Adenocarcinoma and Gastric Adenocarcinoma, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
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 12 inclusion and 39 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: paused, as of the sponsor's last update on 3 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Tumor response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Feb 2023.