Perioperative Immunotherapy vs. Chemo-immunotherapy in Patients With Advanced GC and AEG

NCT04062656 | Unknown Phase 2

• 1 other identifier: CA224-050
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

IMAGINE is a Phase II, randomized, two-arm, chemotherapy controlled modular trial in subjects with histologically confirmed, resectable gastric cancer (GC) or adenocarcinoma of the gastroesophageal junction (AEG). Up to 22 patients will be included in each arm of the trial.

Conditions

Gastric Cancer; Adenocarcinoma of the Esophagogastric Junction

Outcome Measures

Primary Outcomes (1)

• Rate of pathological complete responses

  As determined by pathological examination of the resected tumor following preoperative systemic therapy

  3 years

Secondary Outcomes (9)

• Determination of pathological response rate

  3 years

• Determination of Curative (R0) resection rate

  3 years

• Assessment of disease-free survival rate

  3 years

• Assessment of Survival rate

  3 years

• Evaluation of number of patients with adverse events grade 1 through grade 5 adverse events (AEs), graded according to NCI CTCAE Version 5.0.

  3 years

Study Arms (2)

B - Nivolumab

EXPERIMENTAL

Responders * 6 preoperative cycles nivolumab (i.v., 240mg, q2w) * 4 postoperative cycles nivolumab (i.v., 240mg, q2w) * followed by nivolumab monotherapy for up to one year (i.v., 480mg, q4w) Non-responders * 2 preoperative cycles nivolumab (i.v., 240mg, q2w) * 4 additional cycles nivolumab (i.v., 240mg, q2w)+FLOT (i.v., 240mg, q2w) pre- and postoperative * followed by nivolumab monotherapy for up to one year (i.v., 480 mg, q4w)

Drug: Nivolumab; Drug: Oxaliplatin; Drug: Docetaxel; Drug: 5-Fluorouracil (5-FU); Drug: Folic acid (FA)

D - Nivolumab + relatlimab

EXPERIMENTAL

Responders * 6 preoperative cycles nivolumab (i.v.,240 mg, q2w) and relatlimab (i.v.,80 mg, q2w) * 4 postoperative cycles nivolumab (i.v.,240 mg, q2w) and relatlimab (i.v.,80 mg, q2w) * followed by nivolumab monotherapy for up to one year (i.v., 480mg, q4w) Non-responders * 2 preoperative cycles nivolumab (i.v.,240 mg, q2w) and relatlimab (i.v.,80 mg, q2w) * 4 additional cycles nivolumab (i.v.,240 mg, q2w)+FLOT (i.v.,q2w) pre- and postoperative * followed by nivolumab monotherapy for up to one year (i.v., 480mg, q4w)

Drug: Nivolumab; Drug: relatlimab; Drug: Oxaliplatin; Drug: Docetaxel; Drug: 5-Fluorouracil (5-FU); Drug: Folic acid (FA)

Interventions

Nivolumab DRUG

Nivolumab 240mg administered IV over 30 minutes Nivolumab 480mg should be administered IV over 60 minutes

Also known as: Opdivo

B - Nivolumab; D - Nivolumab + relatlimab

relatlimab DRUG

relatlimab (80mg flat dose) administered IV over 60 min

Also known as: BMS-986016 (Bristol Myer´s Squibb)

D - Nivolumab + relatlimab

Oxaliplatin DRUG

Oxaliplatin 85mg/m² IV over 1 h

Also known as: ELOXATIN

B - Nivolumab; D - Nivolumab + relatlimab

Docetaxel DRUG

Docetaxel 50mg/m² IV over 1 h

Also known as: Taxotere

B - Nivolumab; D - Nivolumab + relatlimab

5-Fluorouracil (5-FU) DRUG

5-fluorouracil 2600mg/m² IV over 24h

Also known as: Adrucil

B - Nivolumab; D - Nivolumab + relatlimab

Folic acid (FA) DRUG

Folic acid 200mg/m² IV over 30 min

Also known as: Leucovorin

B - Nivolumab; D - Nivolumab + relatlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Histologically confirmed, resectable GC or AEG (AEG I-III) (classified per TNM staging system as uT2, uT3, uT4, any N category, M0), or any T N+ M0 Patient (classified per TNM staging system), with the following specifications:
• Measurable target tumors using standard imaging techniques or clinical evaluation and significant FDG-uptake in PET (defined as \[18F\]-FDG-uptake of primary tumor in baseline \>1.35 x liver-SUV + 2 x standard deviation of liver-SUV)
• Female and male patients ≥ 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and for 33 weeks after the end of treatment (males) and for 24 weeks (females) after of treatment. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• ECOG ≤ 1
• Adequate hematological, hepatic and renal function parameters:
• Leukocytes ≥ 2000/mm³, platelets ≥ 100,000/mm³, absolute neutrophil count (ANC) ≥ 1500/µL, hemoglobin ≥ 9 g/dL (5.58 mmol/L)
• Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the upper limit of normal (ULN) (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to randomization
• Serum creatinine ≤ 1.5 x upper limit of normal or calculated creatine clearance of \> 50 mL/min (using Cockroft-Gault formula)
• Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.0 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal, Serum albumin ≥ 2.8 g/dL
• Left ventricular ejection fraction (LVEF) assessment with documented LVEF ≥ 50% by either trans-thoracic echocardiography (TTE) or multigated acquisition (MUGA) (TTE preferred test) within 6 months from first study drug administration
• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures
• Optional, if further IO combination will be added per amendment: positive Biomarker expression (i.e. LAG-3) if data from previous clinical trials support the use of IO combination in selected patients

You may not qualify if:

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment, in particular corticosteroids are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
• Uncontrolled angina within the 3 months prior to consent o Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• QTc prolongation \> 480 msec
• History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, deep venous thrombosis, etc )
• Cardiovascular disease-related requirement for daily supplemental oxygen
• History of two or more MIs OR two or more coronary revascularization procedures
• Subjects with history of myocarditis, regardless of etiology
• Troponin T (TnT) or I (TnI) \> 2 x institutional ULN. Subjects with TnT or TnI levels between \> 1 to 2 x ULN will be permitted if repeat levels within 24 hours are ≤ 1 x ULN. If TnT or TnI levels are \> 1 to 2 x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the coordinating investigator or designee. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the coordinating investigator or designee.
• Active malignancy or a prior malignancy within the past 3 years

Sponsors & Collaborators

• University Hospital, Essen: lead
• GWT-TUD GmbH: collaborator

Study Sites (3)

Uniklinik Köln

Cologne, 50937, Germany

Location

University Hospital Essen

Essen, 45147, Germany

Location

Hämatologisch- Onkologische Praxis Eppendorf (HOPE)

Hamburg, 20249, Germany

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; relatlimab; Oxaliplatin; Docetaxel; Fluorouracil; Folic Acid; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Coenzymes; Enzymes and Coenzymes

Study Officials

• Stefan Kasper-Virchow, Prof.

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: August 20, 2019
• Study Start: September 26, 2019
• Primary Completion: March 1, 2024
• Study Completion: June 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2023-05

Locations

DE (3)