Induction Chemotherapy for Locally Advanced Esophageal Cancer

Induction Chemotherapy for Locally Advanced Esophageal Cancer: A Phase II Study

Evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin) chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease the rate of distant recurrence among patients with locally advanced esophageal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Carcinoma
• Intervention / Treatment: Drug: mFOLFOX6; Combination product: Chemoradiation

Detailed Description

The goal of the study is to evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin) chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease the rate of distant recurrence among patients with locally advanced esophageal cancer. mFOLFOX6 is frequently used to treat metastatic esophageal cancer because of its high response rate in this setting. It has shown promising efficacy in several trials of patients with advanced esophageal cancer and it is the most commonly used combination regimen for this group of patients in the United States.

The investigators propose treating a sample of 40 patients with 3 cycles of induction mFOLFOX6 chemotherapy over six weeks followed by standard chemoradiation and surgery. The investigators hypothesize that patients who undergo induction chemotherapy with mFOLFOX6 prior to standard neoadjuvant chemoradiation and surgery will have a lower rate of distant disease recurrence compared to standard neoadjuvant chemoradiation and surgery.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must have histologically proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia.
2. Must have potentially resectable disease.
3. Must have ECOG performance status 0 or 1.

4. Must have adequate organ function as defined by the following criteria:

   • ANC ≥ 1,500/mm3
   • Platelet count ≥ 100,000/mm3
   • Creatinine (Cr) ≤ 1.5 mg and/or creatinine clearance ≥ 60cc/min.
   • Total bilirubin must be ≤ 1.5 x ULN unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin.
   • Alkaline phosphatase must be ≤ 2 x ULN.
   • AST & ALT must be ≤ 3 x ULN.
5. Men and women of reproductive potential must agree to use an effective contraception method
6. Must be willing and able to provide written informed consent
7. Must be ≥ 18 years or older

Exclusion Criteria:

1. Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor.
2. Known distant metastases.
3. Patients with prior malignancies are eligible if they have been disease-free for > 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.
4. Known ≥ grade 2 neuropathy.
5. Known non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs.
6. Known psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements.
7. Women who are pregnant or nursing.
8. Women and men of reproductive potential who are expecting to conceive or father children.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction Chemotherapy /Chemoradiation; mFOLFOX6 for 3 cycles - Oxaliplatin 85 mg/m2, 5-fluorouracil 2400mg/m2/46 hours, 5-fluorouracil bolus 400mg/m2 and leucovorin 400 mg/m2, then chemoradiation for 5 cycles - Carboplatin AUC 2mg/mL/min, Paclitaxel 50 mg/m2 and radiation therapy.	Drug: mFOLFOX6; Induction Chemotherapy; Other Names: 5-FU; Leucovorin; Oxaliplatin; Combination product: Chemoradiation; Chemoradiation; Other Names: Carboplatin; Paclitaxel; External Beam Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival rate	Evaluate the 2-year disease-free survival rate in patients who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic examination	To assess, by pathologic examination of resected specimen, complete and partial response to induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.	2 years
Toxicities as Assessed by CTCAE v4.0	To determinate the safety and tolerability of induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery. Investigator will collect and record AEs as assessed by CTCAE v4.0. AEs greater than or equal to Grade 3 will be reported as means and number of participants.	25-29 weeks
Overall survival	Evaluate overall survival of participants who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.	2 years
Overall disease-free survival	Evaluate overall disease-free survival in patients who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.	2 years

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Richard Dunne, MD, University of Rochester Wilmot Cancer Center

Publications and helpful links

General Publications

• van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
• Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.
• Ajani JA, Komaki R, Putnam JB, Walsh G, Nesbitt J, Pisters PW, Lynch PM, Vaporciyan A, Smythe R, Lahoti S, Raijman I, Swisher S, Martin FD, Roth JA. A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction. Cancer. 2001 Jul 15;92(2):279-86. doi: 10.1002/1097-0142(20010715)92:23.0.co;2-2.
• Bains MS, Stojadinovic A, Minsky B, Rusch V, Turnbull A, Korst R, Ginsberg R, Kelsen DP, Ilson DH. A phase II trial of preoperative combined-modality therapy for localized esophageal carcinoma: initial results. J Thorac Cardiovasc Surg. 2002 Aug;124(2):270-7. doi: 10.1067/mtc.2002.122545.
• Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, Cohen SJ, Mayer RJ, Venook A, Benson AB 3rd, Goldberg RM. CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers. J Clin Oncol. 2016 Aug 10;34(23):2736-42. doi: 10.1200/JCO.2015.65.5092. Epub 2016 Jul 5.
• Finley KA. Observations of bluegills fed selenium-contaminated Hexagenia nymphs collected from Belews Lake, North Carolina. Bull Environ Contam Toxicol. 1985 Dec;35(6):816-25. doi: 10.1007/BF01636593. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Therapy; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Enzymes and Coenzymes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Radiotherapy; Combined Modality Therapy; Oxaliplatin; Fluorouracil; Carboplatin; Leucovorin; Paclitaxel; Chemoradiotherapy
• Other Study ID Numbers: UGIE 17037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No