mDCF + Avelumab in Resectable Esophago-gastric Adenocarcinoma (EGA)

NCT03288350 | Unknown Phase 2 DMC

• 1 other identifier: MS100070_0073
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, open-label, Simon 2-stage, phase II trial in up to 55 patients with a potentially resectable, histologically-proven, adenocarcinoma or poorly differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of the esophagus. Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5- fluorouracil. Following surgery, pathologic response will be assessed. Patients will then receive adjuvant therapy consisting of 4 cycles of mDCF + avelumab. Patients will be followed to assess two-year disease-free survival rates. The primary objective of this study is to assess the effect on pathologic complete response rate (pCR) of adding avelumab to an mDCF regimen. The secondary objectives of this study are to determine the safety of adding avelumab to an mDCF regimen and assess its effect on two-year disease-free survival.

Conditions

Gastric Adenocarcinoma; Esophageal Adenocarcinoma

Keywords

Phase II Trial; Esophago-Gastric Adenocarcinoma; Avelumab

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR)

  Assessment of the pathologic complete response (pCR) rate after preoperative (neoadjuvant) treatment. pCR has been shown to correlate with long-term outcomes.For the purpose of this study, pCR is considered to represent grade 0 and grade 1 responses, defined by the criteria of the College of American Pathologists.

  30±4 weeks

Secondary Outcomes (2)

• Two-Year Disease Free Survival (DFS)

  104 weeks

• Safety Assessment of Adding Avelumab to mDCF

  104 weeks

Study Arms (1)

mDCF + Avelumab

EXPERIMENTAL

Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil, followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of docetaxel, cisplatin, 5-fluorouracil and avelumab. Docetaxel as a one-hour 40 mg/m2 IV infusion on day 1. Cisplatin 40 mg/m2 IV infusion on day 1. 5-FU 1000 mg/m2/day over 2 days. Avelumab 10 mg/kg following the completion of the mDCF regimen.

Drug: mDCF + Avelumab

Interventions

mDCF + Avelumab DRUG

Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil (mDCF), followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of mDCF and avelumab.

mDCF + Avelumab

Eligibility Criteria

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

You may qualify if:

• Signed, informed consent;
• Age 18 years or older;
• Histological diagnosis of adenocarcinoma or poorly differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of the esophagus;
• The tumour must be deemed by the team to be potentially resectable. This includes imaging studies (detailed below) to clinically stage the tumor and rule out the presence of metastatic disease, and includes a preoperative laparoscopic evaluation for gastric tumors only;
• Stage IB (TlNl only), II, IHA, IIIB;
• Life expectancy greater than 3 months;
• ECOG performance status of 0-1;
• Neutrophils \~ 1500/μL;
• Platelet count\~ 100,000/μL;
• Hemoglobin\~ 9 g/dL;
• Total bilirubin level :S 1.5 x the upper limit of normal (ULN) range unless consistent with Gilbert's syndrome (normal direct bilirubin);
• AST and ALT :S 2.5 x ULN;
• If serum creatinine above upper limit of normal (ULN), creatinine clearance \~ 60 ml/min as determined by 24-h creatinine clearance or Cockcroft-Gault formula;
• Negative pregnancy test for women of child-bearing potential; and
• Highly effective contraception for both male and female subjects throughout the study and for at least 60 days after last avelumab treatment administration if the risk of conception exists.

You may not qualify if:

• Current or prior use of immunosuppressive medication, including corticosteroids, within 7 days prior to registration EXCEPT for the following:
• intranasal, intra-ocular, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection);
• Systemic corticosteroids at physiologic doses :S 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. However, patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;
• Prior organ transplantation, including allogeneic stem cell transplantation;
• Squamous-cell carcinoma diagnosis;
• Significant acute or chronic active infections requiring systemic therapy, including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
• Positive test for HBV surface antigen and I or confirmatory HCV RNA (if anti-HCV antibody tested positive);
• Vaccination with live vaccines within 4 weeks of the first dose of avelumab and while on trial;
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade 2: 3 NCI CTCAE v 4.03) or to any component in avelumab's formulation, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma);
• Known severe hypersensitivity reaction to cisplatin, docetaxel, 5-FU or drugs formulated with polysorbate;
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction(\< 6 months prior to enrollment), unstable angina, congestive heart failure (2: New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication;
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade\> 1 ); however, alopecia, sensory neuropathy Grade :S 2, or other Grade :S 2 not constituting a safety risk based on investigator's judgment are acceptable;

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Publications (1)

• Alcindor T, Tankel J, Fiset PO, Pal S, Opu T, Strasser M, Dehghani M, Bertos N, Zuo D, Mueller C, Cools-Lartigue J, Hickeson M, Marcus V, Camilleri-Broet S, Spatz A, Evaristo G, Farag M, Artho G, Elkrief A, Saleh R, Bailey S, Park M, Huang S, Sangwan V, Ferri L. Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response. Cell Rep Med. 2025 Apr 15;6(4):102045. doi: 10.1016/j.xcrm.2025.102045.

  PMID: 40239627 DERIVED

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

avelumab

Study Officials

• Thierry Alcindor, MD, MSc

  Associate Director, Oncology Clinical Trials

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Touhid Opu, MBBS, MSc

CONTACT

514-934-1934; touhid.opu@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Oncology Clinical Trials

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: September 20, 2017
• Study Start: February 22, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2023
• Last Updated: March 22, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)