Pre-operative capecitabine, oxaliplatin, docetaxel and atezolizumab in gastric cancer (PANDA)

Phase 1

• Conditions: GE junction cancer, gastric cancer; MedDRA version: 20.0Level: LLTClassification code 10017768Term: Gastric cancer stage IV without metastasesSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10066350Term: Adenocarcinoma of the gastrooesophageal junctionSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003854-17-NL
• Lead Sponsor: Antoni van Leeuwenhoek

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-05
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

-Signed informed consent
-Primary resectable, histologically confirmed gastric or GEJ adenocarcinoma
-ECOG performance status of 0 or 1
-Patients age 18 and older
-No signs of distant metastases
-Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
oANC ? 1.5 ? 109/L (1500/?L) without granulocyte colony-stimulating factor support
oLymphocyte count ? 0.5 ? 109/L (500/?L)
oPlatelet count ? 100 ? 109/L (100,000/?L) without transfusion
oHemoglobin ? 5,6mmol/L (patients may be transfused to meet this criterion)
oAST, ALT, and alkaline phosphatase (ALP) ? 2.5 ? upper limit of normal (ULN)
oSerum bilirubin ? 1.5 ? ULN except for patients with known Gilbert disease: serum bilirubin level ? 3 ? ULN
oSerum creatinine ? 1.5 ? ULN or Creatinine clearance ? 40 mL/min (calculated using the Cockcroft-Gault formula)
oSerum albumin ? 25 g/L
oFor patients not receiving therapeutic anticoagulation: INR or aPTT ? 1.5 ? ULN
-For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- CT-scan of thorax and abdomen < 4 weeks to registration. PET-scan and EUS are required for GEJ tumors and are optional for gastric cancers
- For diffuse type gastric cancers, diagnostic laparoscopy should be performed and show no signs of peritoneal metastases
- Patients must be willing to undergo esophagogastroduodenoscopy and biopsies prior to start of treatment and during treatment at defined timepoints
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 147 days prior to the start of treatment;

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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

-Clinical symptoms or radiological suspicion of perforation
-Signs or suspicion of metastatic disease
-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, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis:
Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
-Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
-Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
-Current treatment with anti-viral therapy for HBV
-Treatment with investigational therapy within 28 days prior to initiation of study treatment
-Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies
-Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
-Conditions requiring systemic treatment with either corticosteroids (>10mg 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;
-History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
-Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
-Intercurrent illnesses, including but not limited to infections, that are determined incompatible with the study treatment and protocol by the study team
-Underlying medical conditions that will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination of adverse events
-Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
-History of testing positive human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS);
-History of uncontrolled medical or psychiatric illness. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
-Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within months after the last dose of study treatment
-History of malignancy within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate ? 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

Patients with controlle

Study & Design

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