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

NCT03784326 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0678NCI-2018-02828
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Clinical Stage II Esophageal Adenocarcinoma AJCC v8; Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8; Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8; Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IB Esophageal Adenocarcinoma AJCC v8; 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; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (PathCR)

  The optimum two-stage design proposed by Simon will be implemented. The PathCR rate will be estimated along with the exact 95% confidence interval.

  Up to 3 years

Secondary Outcomes (5)

• Disease-free survival (DFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Changes in tumor stroma profile after treatment

  Baseline up to 3 years

• 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

• Tumor regression determined by CT or MRI

  Baseline up to 3 years

Study Arms (2)

Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU)

EXPERIMENTAL

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

Drug: Atezolizumab; Procedure: Conventional Surgery; Drug: Fluorouracil; Drug: Oxaliplatin

Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

EXPERIMENTAL

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.

Drug: Atezolizumab; Procedure: Conventional Surgery; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Given IV (vein)

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU); Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

Conventional Surgery PROCEDURE

Undergo surgical resection

Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU); Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

Fluorouracil DRUG

Given IV (vein)

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU); Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

Oxaliplatin DRUG

Given IV (vein)

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Cohort 1-Atezolizumab combination with Oxaliplatin and 5-fluorouracil (5-FU); Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

Tiragolumab DRUG

Given IV (vein)

Cohort 2- Atezolizumab plus and Tiragolumab with Oxaliplatin and 5-fluorouracil (5-FU)

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 Form
• Age ≥ 18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically or cytologically confirmed esophageal or gastroesophageal type I or II adenocarcinoma
• No prior therapy including chemotherapy or radiation therapy.
• Patients with T1N1, and T2-3 with any N will be eligible.
• ECOG Performance Status of 0-1
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• ANC ≥ 1.5 x 109/L (1500/L) without granulocyte colony-stimulating factor support
• Lymphocyte count ≥ 0.5 x 109/L (500/L)
• Platelet count ≥ 100 x 109/L (100,000/L) without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL) Patients may be transfused to meet this criterion.
• AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN with the following exception:
• Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN

You may not qualify if:

• Patients with T1aN0, T4b, or metastatic cancer will be excluded.
• Squamous cell carcinoma histology
• Invasion into nearby organs (T4b) with or increased risk for fistula
• Significant comorbid conditions (defined as uncontrolled diabetes, active angina or heart failure, uncontrolled hypertension (\>160 mmHg systolic or ≥100 mmHg diastolic) or increased risk of prolonged QTc (QTc \> 500 ms), or active psychiatric condition that prevents consistent participation and compliance).
• More than grade 1 neuropathy.
• Unable to comprehend the requirements of the study or comply with it.
• Active bleeding from primary tumor requiring radiation therapy.
• History of leptomeningeal disease
• Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• 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's syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

atezolizumab; Fluorouracil; dehydroftorafur; Oxaliplatin; Tiragolumab

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Mariela Blum

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: December 21, 2018
• Study Start: February 19, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-01

Locations

US (1)