Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
- Conditions
- Oesophageal AdenocarcinomaGastric Adenocarcinoma
- Registration Number
- NCT05135845
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief 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. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 90
- 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.
- 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
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Tumor response 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.
- Secondary Outcome Measures
Name Time Method Duration of overall response 24 months 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
Time to response 24 months 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
Progression-free survival 24 months 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.
Overall survival 24 months Time between inclusion and death (any cause) or last follow-up (maximum=24 months), whichever occurs first
Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration Day 42 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 AEProportion of unacceptable toxicity of the regimen during the whole treatment course 12 months or treatment discontinuation 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 AEProportion of patients with adverse events during the whole treatment course 12 months or treatment discontinuation All adverse events during the whole treatment course
Trial Locations
- Locations (7)
Centre François Leclerc
🇫🇷Dijon, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut Universitaire du Cancer
🇫🇷Toulouse, France
Hôpital Jean Minjoz
🇫🇷Besançon, France
Hôpital Haut Lévêque
🇫🇷Pessac, France
AP-HP Hôpital Saint Louis
🇫🇷Paris, France
Institut Gustave Roussy
🇫🇷Villejuif, France