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Induction Chemotherapy for Locally Advanced Esophageal Cancer

Primary Purpose

Esophageal Carcinoma

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

mFOLFOX6

Chemoradiation

About this trial

This is an interventional treatment trial for Esophageal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must have histologically proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia.
Must have potentially resectable disease.
Must have ECOG performance status 0 or 1.
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.
Men and women of reproductive potential must agree to use an effective contraception method
Must be willing and able to provide written informed consent
Must be ≥ 18 years or older

Exclusion Criteria:

Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor.
Known distant metastases.
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.
Known ≥ grade 2 neuropathy.
Known non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs.
Known psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements.
Women who are pregnant or nursing.
Women and men of reproductive potential who are expecting to conceive or father children.

Sites / Locations

University of Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction Chemotherapy /Chemoradiation

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Overall survival

Evaluate overall survival of participants who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Overall disease-free survival

Evaluate overall disease-free survival in patients who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Full Information

NCT ID

NCT03110926

First Posted

March 30, 2017

Last Updated

August 9, 2023

Sponsor

University of Rochester

1. Study Identification

Unique Protocol Identification Number

NCT03110926

Brief Title

Induction Chemotherapy for Locally Advanced Esophageal Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 19, 2017 (Actual)

Primary Completion Date

June 12, 2024 (Anticipated)

Study Completion Date

June 12, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rochester

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Induction Chemotherapy /Chemoradiation

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

mFOLFOX6

Other Intervention Name(s)

Oxaliplatin, Leucovorin, 5-FU

Intervention Description

Induction Chemotherapy

Intervention Type

Combination Product

Intervention Name(s)

Chemoradiation

Other Intervention Name(s)

Carboplatin, Paclitaxel, External Beam Radiation Therapy

Intervention Description

Chemoradiation

Primary Outcome Measure Information:

Title

Disease-free survival rate

Description

Evaluate the 2-year disease-free survival rate in patients who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Pathologic examination

Description

To assess, by pathologic examination of resected specimen, complete and partial response to induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Time Frame

2 years

Title

Toxicities as Assessed by CTCAE v4.0

Description

Time Frame

25-29 weeks

Title

Overall survival

Description

Evaluate overall survival of participants who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Time Frame

2 years

Title

Overall disease-free survival

Description

Evaluate overall disease-free survival in patients who receive induction chemotherapy with mFOLFOX6 followed by standard chemoradiation and surgery.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Must have histologically proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia. Must have potentially resectable disease. Must have ECOG performance status 0 or 1. 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. Men and women of reproductive potential must agree to use an effective contraception method Must be willing and able to provide written informed consent Must be ≥ 18 years or older Exclusion Criteria: Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor. Known distant metastases. 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. Known ≥ grade 2 neuropathy. Known non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs. Known psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements. Women who are pregnant or nursing. Women and men of reproductive potential who are expecting to conceive or father children.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard Dunne, MD

Organizational Affiliation

University of Rochester Wilmot Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Rochester

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

22646630

Citation

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.

Results Reference

background

PubMed Identifier

26254683

Citation

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.

Results Reference

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PubMed Identifier

11466680

Citation

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.

Results Reference

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PubMed Identifier

12167786

Citation

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.

Results Reference

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PubMed Identifier

27382098

Citation

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.

Results Reference

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PubMed Identifier

24982764

Citation

Lloyd S, Chang BW. Current strategies in chemoradiation for esophageal cancer. J Gastrointest Oncol. 2014 Jun;5(3):156-65. doi: 10.3978/j.issn.2078-6891.2014.033.

Results Reference

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Induction Chemotherapy for Locally Advanced Esophageal Cancer

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