Postoperative Immunotherapy vs Standard Chemotherapy for Gastric Cancer With High Risk for Recurrence

Patrocinador principal: European Organisation for Research and Treatment of Cancer - EORTC

The primary objective of the trial is to investigate if nivolumab plus ipilimumab given as adjuvant treatment improve disease free survival (DFS) in patients with stage Ib-IVa gastric and esophagogastric junction adenocarcinoma and high risk of recurrence (defined by ypN1-3 and/or R1 status) following neoadjuvant chemotherapy and resection.

Other study objectives:

- To investigate the safety and effect of adjuvant immunotherapy on long term oncologic outcomes and quality of life of patients in the study

- To correlate nutritional status assessment on outcomes and quality of life of patients

• Gastric and Esophagogastric Junction Adenocarcinoma

Tipo de intervención: Drug

Nombre de intervención: Nivolumab and Ipilimumab

Descripción: Nivolumab 1 mg/kg IV Q3W plus Ipilimumab 3 mg/kg IV Q3W for 4 cycles (3 months) followed by nivolumab 240 mg flat-dose IV Q2W for 9 months.Total treatment time 1 year

Etiqueta de grupo de brazo: immunotherapy arm

Tipo de intervención: Other

Nombre de intervención: chemotherapy

Descripción: Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).

Etiqueta de grupo de brazo: chemotherapy arm

Criterios:

Inclusion Criteria:

- Histologically proven gastric, lower esophageal or GE-junction adenocarcinoma (Siewert I-III)

- Subjects must have completed pre-operative chemotherapy with a fluoropyrimidine-platinum containing regimen and macroscopically complete surgery prior to randomization

- Minimal duration of neoadjuvant chemotherapy should be 6 weeks, maximum 12 weeks.

- Total or distal gastrectomy with D2 lymphadenectomy according to ESMO guidelines should have been completed for gastric and junctional Siewert type III cancers. Ivor Lewis or McKeown oesophagectomy with two field lymphadenectomy should have been performed for junctional Siewert type I cancers. For Siewert type II cancers either total gastrectomy with D2-lymphadenectomy or oesophagectomy with two field lymphadenectomy should have been completed. Open, minimal invasive or hybrid surgical approaches are acceptable as long as the requirements above are fulfilled.

- Regardless of the type of surgery a minimum of 15 lymph nodes should have been resected and examined.

- Recovered from surgery and fit for study treatment as assessed by a multidisciplinary team. Ideally, surgery should have been completed 1 month before at the maximum.

- ypN1-3 status according to current (8th) version of TNM classification system. In case of an ypN0 status patients must meet the inclusion criterion of R1 resection.

- R0 or R1 resection according to current (8th) version of TNM classification system. In case of R0 resection, patients must meet the inclusion criterion of ypN1-3

- Availability of operative and pathology reports for review

- WHO performance status score of 0 or 1

- Age ≥ 18 years

- Adequate organ function assessed within 7 days before randomization:

- White blood cell count (WBC) > 2 x 109/L

- Absolute neutrophil count (ANC) > 1.5 x 109/L

- Platelets ≥ 100 x 109/L

- Hemoglobin ≥ 9 g/dL

- Measured/calculated creatinine clearance ≥ 60 mL/min (according to Cockroft-Gault formula).

- Total bilirubin within normal limits (if the patient has documented Gilbert's disease ≤ 1.5 * ULN or direct bilirubin ≤ ULN)

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5ULN

- All toxicities (exception alopecia) attributed to prior anti-cancer therapy must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.

- Availability of tumor tissue from the resected site of disease must be provided for biobanking

- Women of childbearing potential (WOCBP*) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 24 hours prior to randomization

- Patients of childbearing / reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least 5 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

- Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last study treatment.

- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

- R2 resection status

- M1 stage according to current (8th) version of TNM classification system

- Patients who have undergone complete resection of metastases

- Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for postoperative chemotherapy or immunotherapy

- Subjects with previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry. Adequately treated cervical carcinoma in situ, and localized non-melanoma skin cancer are no exclusion criteria, regardless of timepoint of diagnosis.

- Subjects with active, known, or suspected infectious or autoimmune disease

- Patients who have received antibiotics within the last 14 days before randomization are excluded.

- Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll

- Subjects with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration

- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

- Subjects with > Grade 1 peripheral neuropathy

- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

- Prior or concomitant treatment with radiotherapy/radiochemotherapy

- Any positive test result for HBV or HCV indicating acute or chronic infection

- Known history of testing positive for HIV or known AIDS

- Known uncontrollable hypersensitivity to the components of cisplatin/oxaliplatin, fluorouracil (5-FU) or capecitabine, epirubicine or docetaxel

- Known dihydropyrimidine dehydrogenase (DPD) deficiency

- Ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine.

Género: All

Edad mínima: N/A

Edad máxima: N/A

Voluntarios Saludables: No

Apellido: EORTC HQ

Teléfono: +32 2 774 16 11

Email: [email protected]

Czechia

France

Germany

Israel

Italy

Norway

Poland

Portugal

Spain

United Kingdom

January 2020

Tipo: Sponsor

• Adenocarcinoma
• Recurrence

Etiqueta: chemotherapy arm

Tipo: Other

Descripción: Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).

Etiqueta: immunotherapy arm

Tipo: Experimental

Descripción: Treatment: Nivolumab 1 mg/kg IV Q3W plus Ipilimumab 3 mg/kg IV Q3W for 4 cycles (3 months) followed by nivolumab 240 mg flat-dose IV Q2W for 9 months.Total treatment time 1 year. No chemotherapy.

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Treatment

Enmascaramiento: None (Open Label)