Phase I/II Study of Perioperative Chemotherapy Plus Immunotherapy Followed by Surgery in Localized Esophageal and Gastroesophageal Adenocarcinoma

Phase 2

Recruiting

• Conditions: Pathologic Stage IB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IC Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage II Esophageal Adenocarcinoma AJCC v8; Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage III Esophageal Adenocarcinoma AJCC v8
• Interventions: Drug: Atezolizumab; Procedure: Conventional Surgery; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Tiragolumab

• Registration Number: NCT03784326
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

To learn if atezolizumab in combination with oxaliplatin and 5-fluorouracil (5-FU), when given before surgery, can help to control esophageal and/or gastroesophageal cancer. To learn if adding tiragolumab to the above drug combination can help to control the disease.

Detailed Description

Primary Objectives:

* Atezolizumab +/- tiragolumab in combination with oxaliplatin and 5-fluorouracil (modified FOLFOX) therapy in the neoadjuvant setting will achieve a pathological complete response of approximately 20% in patients with localized esophageal and gastroesophageal (GEJ) adenocarcinoma.

Secondary Objectives:

* To evaluate safety and toxicity profile of intravenous Atezolizumab +/- Tiragolumab in combination with Oxaliplatin and 5-FU chemotherapy as neoadjuvant treatment for resectable esophageal or GEJ adenocarcinoma.

* To assess the efficacy of the combination by tumor regression grade scoring in the surgical specimen.

* To assess the overall safety and tolerability of adjuvant Atezolizumab +/- Tiragolumab in subjects with resected esophageal and GEJ cancer

* To evaluate disease free survival (DFS) and overall survival (OS) in cohort 1 and cohort 2

* To explore changes in tumor stroma profile before and after immunotherapy in combination with chemotherapy

Study Timeline

• Study First Submitted: 2018-12-13
• Study First Submitted QC: 2018-12-20
• Study First Posted: 2018-12-21
• Study Start: 2019-02-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-23
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU)	Atezolizumab	The combination of Atezolizumab with Oxaliplatin and 5-Fluorouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab on Day 1 of each 21-day cycle for total of 24 weeks
Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU)	Conventional Surgery	The combination of Atezolizumab with Oxaliplatin and 5-Fluorouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab on Day 1 of each 21-day cycle for total of 24 weeks
Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)	Tiragolumab	The combination of Atezolizumab + Tiragolumab with Oxaliplatin and 5-Flourouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab + Tiragolumab on Day 1 of each 21-day cycle for a total of 48 weeks.
Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)	Conventional Surgery	The combination of Atezolizumab + Tiragolumab with Oxaliplatin and 5-Flourouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab + Tiragolumab on Day 1 of each 21-day cycle for a total of 48 weeks.
Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU)	Fluorouracil	The combination of Atezolizumab with Oxaliplatin and 5-Fluorouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab on Day 1 of each 21-day cycle for total of 24 weeks
Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU)	Oxaliplatin	The combination of Atezolizumab with Oxaliplatin and 5-Fluorouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab on Day 1 of each 21-day cycle for total of 24 weeks
Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)	Atezolizumab	The combination of Atezolizumab + Tiragolumab with Oxaliplatin and 5-Flourouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab + Tiragolumab on Day 1 of each 21-day cycle for a total of 48 weeks.
Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)	Fluorouracil	The combination of Atezolizumab + Tiragolumab with Oxaliplatin and 5-Flourouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab + Tiragolumab on Day 1 of each 21-day cycle for a total of 48 weeks.
Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)	Oxaliplatin	The combination of Atezolizumab + Tiragolumab with Oxaliplatin and 5-Flourouracil IV on Days 1 and 15 of each 28-day cycle for total of 6 doses followed by surgery followed by Atezolizumab + Tiragolumab on Day 1 of each 21-day cycle for a total of 48 weeks.

Primary Outcome Measures

Name	Time	Method
Pathological complete response (PathCR)	Up to 3 years	The optimum two-stage design proposed by Simon will be implemented. The PathCR rate will be estimated along with the exact 95% confidence interval.

Secondary Outcome Measures

Name	Time	Method
Changes in tumor stroma profile after treatment	Baseline up to 3 years	The changes in tumor stroma profile after treatment assessed through paired t-tests or Wilcoxon signed rank tests if normality assumption is not satisfied.
Incidence of toxicities defined as any treatment-related grade 3 or greater non-hematologic adverse events (AEs) determined by CTCAE version v 4.03.	From the start of study treatment up to 3 months
Disease-free survival (DFS)	Up to 3 years	The Kaplan-Meier method will be used to estimate the probabilities of DFS.
Overall survival (OS)	Up to 3 years	The Kaplan-Meier method will be used to estimate the probabilities of OS.
Tumor regression determined by CT or MRI	Baseline up to 3 years

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States