Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GEJC) – MONEO Study

Phase 1

• Conditions: Resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC); MedDRA version: 20.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000782-21-ES
• Lead Sponsor: Vall d' Hebron Institute of Oncology (VHIO)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-30
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 37

Inclusion Criteria

1.Histologically proven, gastric or GEJ adenocarcinoma (Siewert I-III).
2.Availability of a paraffin block from the diagnostic endoscopic biopsy (and a fresh biopsy if possible), and a second tumor block (fresh + paraffin) from the surgical specimen.
3.Have evaluable disease as defined by RECIST 1.1 and determined by investigator assessment, with the absence of distant metastases on CT scan of thorax, abdomen and pelvis.
4.Patient medically fit and amenable to gastrectomy/esophagectomy with curative intent as confirmed by a multidisciplinary team discussion.
5.UICC tumor stage Ib (T1N1 only, T2N0 not eligible) to IIIC, as defined by CT, according to the 7th AJCC Edition.
6.Age = 18 years.
7.WHO performance status 0-1.
8.Adequate organ function (assessed within 7 days prior treatment initiation):
a.White blood cell count (WBC) > 3 x 109 /L
b.Absolute neutrophil count (ANC) > 1.5 x 109 /L
c.Platelets = 100 x 109 /L
d.Estimated glomerular filtration rate should be > 50 ml/min
e.Total bilirubin within normal limits (if the patient has documented Gilbert’s disease = 1.5 x ULN or direct bilirubin = ULN).
f.Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN.
9.In case of anticoagulation, investigator and patient should agree to replace any oral anticoagulation by subcutaneous administration of low-molecular weight heparin in equivalent doses before treatment start;
10.For women who are not postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last treatment dose
11.For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods for contraception.
12.For all female patients who are not confirmed postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) a negative serum pregnancy test (ß-human chorionic gonadotropin [ß-hCG]) result should be available before treatment and within 7 days from treatment start should be performed. Female patients should not be breast feeding.
13.Written informed consent must be given according to ICH/GCP, and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion Criteria

1.Other histology different from adenocarcinoma.
2.Has had previous therapy for gastric or GEJ cancer.
3.Known hypersensitivity to the components of anti-PD-L1, docetaxel, oxaliplatin, fluorouracil/leucovorin.
4.Known dihydropyrimidine dehydrogenase (DPD) deficiency.
5.Previous malignancy within the last 5 years, except for adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated cancer without impact on the patient’s overall prognosis according to the judgment of the investigator.
6.Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those condition should be discussed with the patient before registration in the trial.
7.History of clinically significant comorbidities.
8.Patients medically unfit for FLOT chemotherapy, according to the local guidance.
9.Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10.Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). History or evidence of interstitial lung disease or active, non-infectious pneumonitis.
11.Active infection requiring systemic therapy.
12.Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Test for HBV and HCV are required for the screening.
13.Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu-vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.
14.Prior organ transplantation including allogenic stem-cell transplantation.
15.Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v4.0 Grade = 3).
16.Persisting toxicity related to prior therapy (NCI-CTCAE v4.0 Grade > 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable.
17.Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified