Durvalumab, an Anti-PDLI Antibody, and Tremelimumab, an Anti-CTLA4 Antibody, and Chemoradiation Before Surgery for Esophageal Cancer

NCT02962063 | Active Not Recruiting Phase 1

• 1 other identifier: 16-1405
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of adding a new drug, durvalumab (also called MEDI4736), to chemoradiation with either FOLFOX/Capeox or carboplatin and paclitaxel, following initial chemotherapy with FOLFOX. The investigators want to find out what effects, good and/or bad, this combination has on the patient and cancer.

Conditions

Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Durvalumab; Anti-PD-L1 Antibody; Tremelimumab; 16-1405

Outcome Measures

Primary Outcomes (2)

• unacceptable toxicity

  "Unacceptable toxicity" is defined as any of the following toxicities: \>1 episode of grade 3/4 neutropenia or thrombocytopenia \<75,000/μL (despite prior dose reduction) during chemoradiation any toxicity that results in \>2 week cumulative delay in chemoradiation any toxicity that is attributed to durvalumab which results in a delay of \>8 weeks in surgery, i.e. surgery \>16 weeks from the end of radiation, for a potentially operable patient any reason that is attributed to durvalumab which leads to death within 30 days of surgery. All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria, version 4.0.3.

  1 year

• pathologic complete response rate

  1 year

Secondary Outcomes (1)

• overall survival (OS)

  3 years

Study Arms (1)

Esophageal Cancer

EXPERIMENTAL

This is a phase Ib/II trial of durvalumab (MEDI4736), a monoclonal antibody against programmed death ligand-1 (PD-L1)), and tremelimumab, an anti-CTLA-4 antibody, in combination with chemoradiation for patients with locally advanced (TanyN+M0 or T3-4NanyM0) esophageal or gastroesophageal (GE) junction adenocarcinoma.

Biological: durvalumab; Drug: carboplatin AUC 2/paclitaxel; Radiation: External beam radiation (EBRT); Procedure: esophagogastrectomy; Drug: Tremelimumab

Interventions

durvalumab BIOLOGICAL

Durvalumab can be given irrespective of CBC, at the discretion of the treating physician.

Also known as: (MEDI4736)

Esophageal Cancer

carboplatin AUC 2/paclitaxel DRUG

Esophageal Cancer

External beam radiation (EBRT) RADIATION

Radiation will be delivered starting on a Monday or Tuesday between Days 29-30, based on the first induction durvalumab dose administered on Day 1. Patients will be treated 5 days/week at 1.80 Gy/day, to a total planned dose of 41Gy in 23 fractions. Induction Day 15 has a -1/+2 day window, and Day 29 has a -1/+1 day window.

Esophageal Cancer

esophagogastrectomy PROCEDURE

Patients undergo surgical resection 6-10 weeks after the completion of chemoradiation.

Esophageal Cancer

Tremelimumab DRUG

Tremelimumab will be administered once at 300 mg on Day 29 prior to chemoradiation only.

Esophageal Cancer

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). Pathology must be confirmed at Memorial Sloan Kettering Cancer Center
• Tumors that are Her2 positive are eligible
• Availability of archived tumor tissue for banking
• TanyN+M0 or T3-4NanyM0 tumors
• Disease must be clinically limited to the esophagus or GEJ. GEJ tumors must be Siewert Type I-III
• No prior chemotherapy
• Prior radiation is permitted, provided it does not limit the ability to deliver per-protocol radiation in the opinion of the treating radiation oncologist
• Patients must have surgically resectable disease treatable by esophagectomy, as assessed by a thoracic surgeon
• mSUV in the primary tumor must be ≥5.0
• Patients must be ≥18 years of age
• Eastern Cooperative Oncology Group performance status of 0-1
• Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause;
• OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
• Adequate organ function defined at baseline as:
• WBC ≥3,000/ L

You may not qualify if:

• Carcinoma in-situ and tumors determined to be T1-2N0
• Tumors with significant involvement of the proximal stomach which, in the opinion of the treating thoracic surgeon, would require an esophagogastrectomy
• Patients with evidence of metastatic disease, including:
• Positive malignant cytology of the pleural, pericardium or peritoneum
• Radiographic evidence of distant organ involvement
• Non-regional lymph nodes that cannot be contained within a radiation field
• Biopsy-proven tumor invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. Recurrent laryngeal or phrenic nerve paralysis
• Grade 2 ≥ peripheral neuropathy
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• History of pneumonitis
• The use of immunosuppressive medication within 28 days prior to the first dose of durvalumab-/tremelimumab. The following are exceptions to this criterion:
• Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g. intraarticular injection)
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

durvalumab; tremelimumab

Study Officials

• Geoffrey Ku, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase Ib/II trial of durvalumab (MEDI4736), a monoclonal antibody against programmed death ligand-1 (PD-L1)), and tremelimumab, an anti-CTLA-4 antibody, in combination with chemoradiation for patients with locally advanced (TanyN+M0 or T3-4NanyM0) esophageal or gastroesophageal (GE) junction adenocarcinoma.

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: November 11, 2016
• Study Start: November 1, 2016
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

US (7)