Clinical trial NCT05135845: Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
Official title: Phase II Trial to Evaluate the Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Oesophageal Adenocarcinoma
Gastric Adenocarcinoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-11-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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).
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Tumor response
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration
timeFrame: Day 42
measure: Proportion of unacceptable toxicity of the regimen during the whole treatment course
timeFrame: 12 months or treatment discontinuation
measure: Proportion of patients with adverse events during the whole treatment course
timeFrame: 12 months or treatment discontinuation
measure: Duration of overall response
timeFrame: 24 months
measure: Time to response
timeFrame: 24 months
measure: Progression-free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: Dijon
country: France
facility: Centre François Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Paris
country: France
facility: AP-HP Hôpital Saint Louis
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Toulouse
country: France
facility: Institut Universitaire du Cancer
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: