Phase II Study of Avelumab Plus Chemotherapy in the Peri-operative Treatment for Patients With Resectable Gastric Cancer (GC) or Gastroesophageal Junction Cancer (GEJC)

NCT03979131 | Active Not Recruiting Phase 2

• 1 other identifier: VHIO19001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC) The addition of Avelumab to the perioperative chemotherapy in GC and GEJC patients may increase pathological responses by a synergic effect activating the immune response. Conclusively, the survival of these patients would improve. The primary objective is to investigate whether the addition of avelumab to FLOT chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) improves efficacy in terms of pathological complete response (pCR) rate, in GC and GEJC patients compared to the historical data of chemotherapy alone in the neoadjuvant setting.

Conditions

Gastroesophageal Junction Adenocarcinoma; Stomach Neoplasms

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Pathological complete response (pCR) rate, where pCR is defined as the absence of residual tumor based on evaluation of the resected esophagogastric specimen according to Becker remission criteria

  7 years

Secondary Outcomes (4)

• Overall survival (OS)

  7 years

• Disease-free survival (DFS)

  7 years

• Progression-free survival (PFS)

  7 years

• Surgical complete resection rate (R0)

  2 years

Study Arms (1)

Resectable GC and GEJC+avelumab+FLOT preoperative treatment

EXPERIMENTAL

Peri-operatory treatment consisting of four cycles (each cycle is 14 days) of neoadjuvant chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) plus avelumab previous to surgery. Surgery is recommended to be scheduled 4 to 6 weeks after the last dose. Afterwards (4 to 10 weeks after surgery), four cycles of adjuvant therapy with the same schema, followed by avelumab up to one year.

Combination Product: Avelumab addition to perioperative chemotherapy in GC and GEJC

Interventions

Avelumab addition to perioperative chemotherapy in GC and GEJC COMBINATION_PRODUCT

Avelumab addition to perioperative chemotherapy in GC and GEJC. Peri-operatory treatment consisting of four cycles (each cycle is 14 days) of neoadjuvant chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) plus avelumab previous to surgery. Surgery is recommended to be scheduled 4 to 6 weeks after the last dose. Afterwards (4 to 10 weeks after surgery), four cycles of adjuvant therapy with the same schema, followed by avelumab up to one year. There will be be a follow-up of 5 years.

Resectable GC and GEJC+avelumab+FLOT preoperative treatment

Eligibility Criteria

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

You may qualify if:

• Histologically proven, gastric or GEJ adenocarcinoma (Siewert I-III).
• 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.
• 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.
• Patient medically fit and amenable to gastrectomy/esophagectomy with curative intent as confirmed by a multidisciplinary team discussion.
• UICC tumor stage Ib (T1N1 only, T2N0 not eligible) to IIIC, as defined by CT, according to the 7th AJCC Edition.
• Age ≥ 18 years.
• WHO performance status 0-1.
• Adequate organ function (assessed within 7 days prior treatment initiation):
• White blood cell count (WBC) \> 3 x 109 /L
• Absolute neutrophil count (ANC) \> 1.5 x 109 /L
• Platelets ≥ 100 x 109 /L
• Estimated glomerular filtration rate should be \> 50 ml/min
• Total bilirubin within normal limits (if the patient has documented Gilbert's disease ≤ 1.5 x ULN or direct bilirubin ≤ ULN).
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
• 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;

You may not qualify if:

• Other histology different from adenocarcinoma.
• Has had previous therapy for gastric or GEJ cancer.
• Known hypersensitivity to the components of anti-PD-L1, docetaxel, oxaliplatin, fluorouracil/leucovorin.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• 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.
• 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.
• History of clinically significant comorbidities.
• Patients medically unfit for FLOT chemotherapy, according to the local guidance.
• 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.
• 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.
• Active infection requiring systemic therapy.
• 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.
• 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.
• Prior organ transplantation including allogenic stem-cell transplantation.
• 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).

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (1)

Vall d'Hebron Institute of Oncology

Barcelona, Spain

Location

Related Publications (1)

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• María Alsina Maqueda, PhD

  Vall d'Hebron Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is an open-label, non-randomized, multicentric phase II clinical trial in subjects with operable gastric or GEJ adenocarcinoma. Tissue biopsies before and after treatment will be required. Blood samples will be required at different points of the treatment for biomarker analyses. Tumor imaging assessments will be performed at baseline, after the neoadjuvant treatment, and after finalizing the adjuvancy with avelumab/FLOT, and every 6 months thereafter to determine response to treatment. Clinical decision making will be based on Investigator assessment of the scans using RECIST v1.1. Safety of avelumab/FLOT will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 7, 2019
• Study Start: August 22, 2019
• Primary Completion: March 15, 2023
• Study Completion (Estimated): June 15, 2026
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)