NCT00525915

Brief Summary

The goal of this clinical research study is to learn if a combination of the investigational drug oxaliplatin with 5-Fluorouracil (5-FU) (given at the same time as radiation therapy) is as effective as a combination of these two drugs given before and during radiation therapy in the treatment of esophageal or gastroesophageal cancers. The safety of these combinations of therapy will also be compared. Objectives: Primary objective: Compare the Pathologic Complete Response rate and % of patients with \<50% residual cancer in the resected surgical specimen between Arms A and B. Secondary objectives:

  1. 1.Compare 1-year and 3-year survival rates, median survival time, R0 resection rates, safety, and local plus systemic relapse rates between Arms A and B
  2. 2.Perform exploratory correlative studies on blood, adjacent normal and cancer tissue to assess predictive markers of response and outcome.
  3. 3.Evaluate the joint effects, including possible interactive effects, of proton-versus-photon therapy and treatment arm on overall survival, R0 resection rates, safety, and local plus systemic relapse rates.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2005

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2005

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

September 4, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 6, 2007

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

February 9, 2015

Completed
Last Updated

February 9, 2015

Status Verified

January 1, 2015

Enrollment Period

7.9 years

First QC Date

September 4, 2007

Results QC Date

January 27, 2015

Last Update Submit

January 27, 2015

Conditions

Keywords

Esophageal CancerGastroesophageal CancerGastroesophageal JunctionRadiation Therapy5-Fluorouracil5-FUAdrucilEfudexOxaliplatin

Outcome Measures

Primary Outcomes (1)

  • Pathologic Complete Response Rate

    Pathologic Complete Response rate: percentage of participants with response reported as Pathologic complete response (pathCR) following surgery. Once surgery performed, response to therapy judged in surgical specimen with three possible categories reported: 1) Pathologic complete response (no residual cancer in the specimen); 2) \<50% of residual cells in the surgical specimen; or 3) \>50% of cells in the surgical specimen. Upon recovery from chemoradiation (Chemo), surgery follows approximately 5-6 weeks later with response assessment. Arm A schedule consists of 6 weeks of Chemo +XRT, followed by 5-6 weeks of rest, followed by surgery. Arm B schedule consist of 8 weeks of Chemo, followed by 6 weeks of Chemo +XRT, followed by 5-6 weeks of rest, followed by surgery. In particular, Arm B is 8 weeks longer than Arm A.

    Surgery post chemotherapy (approximately 10-11 weeks)

Study Arms (2)

Arm A: Chemo with Radiation Treatment

EXPERIMENTAL

For 5 weeks, Chemo of 5-FU 250 mg/m\^2 intravenous (IV) over 24 hours for 5 days weekly with Oxaliplatin 40 mg/m\^2 IV daily over 2 hours, and Radiation treatment every weekday; then surgery.

Drug: 5-FluorouracilDrug: OxaliplatinRadiation: Radiation TherapyProcedure: Surgery

Arm B: Pre-Op Chemo + Chemo with Radiation Treatment

EXPERIMENTAL

Pre-Operative Chemo 5-FU 2.2 mg/m\^2 IV continuous infusion over 48 hours start on day 1 and 15, and Oxaliplatin 100 mg/m\^2 IV on day 1 and 15; followed by Surgery + Chemo with Radiation Therapy (same as Arm A)

Drug: 5-FluorouracilDrug: OxaliplatinRadiation: Radiation TherapyProcedure: Surgery

Interventions

Arm A = 250 mg/m\^2 IV over 24 hours for 5 days weekly for 5 weeks. Arm B = 2.2 mg/m\^2 IV over 48 hours on days 1 and 15.

Also known as: 5-FU, Adrucil, Efudex
Arm A: Chemo with Radiation TreatmentArm B: Pre-Op Chemo + Chemo with Radiation Treatment

Arm A: 40 mg/m\^2 IV daily over 2 hours for 5 weeks Arm B: 100 mg/m\^2 IV on Day 1 and 15

Also known as: Eloxatin
Arm A: Chemo with Radiation TreatmentArm B: Pre-Op Chemo + Chemo with Radiation Treatment

Radiation treatment every weekday for 5 weeks.

Also known as: RT, XRT
Arm A: Chemo with Radiation TreatmentArm B: Pre-Op Chemo + Chemo with Radiation Treatment
SurgeryPROCEDURE

Surgical removal of the primary tumor and lymph nodes following completion of disease status evaluation post chemotherapy and radiation treatments.

Arm A: Chemo with Radiation TreatmentArm B: Pre-Op Chemo + Chemo with Radiation Treatment

Eligibility Criteria

Age18 Years - 76 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Local regional carcinoma of the thoracic esophagus (squamous cell or adeno) or gastroesophageal junction.
  • Patients with T1N1, and T2-3 with any N (M1a only) will be eligible.
  • Normal liver (serum glutamic-pyruvic transaminase (SGPT) \< 56µL, Total Bilirubin \<1.5 mg/dL), kidney (Creatinine \<1.75 mg/dL), and bone marrow functions (AGN \>1,500µL, platelet count \>100,000/µL).
  • Performance status 0 or 1.
  • Signed informed consent by the investigator or their designee and patient.
  • Medically fit for surgery.
  • No Celiac (except for the GE junction cancers), supraclavicular, or paraaortic nodal enlargement unless biopsy negative.
  • None of the celiac nodes should be larger than 2 cm
  • Male or Female but both sexes must practice adequate contraception while on therapy
  • \>/=18 years but less than 76 years
  • No known allergy to any of the study drugs.
  • No prior therapy for this cancer.
  • No significant cancer (defined as non-melanomatous skin cancers and treated cervical cancers) within the past 5 years
  • New York Heart Association (NYHA) I and II

You may not qualify if:

  • Patients with T1N0, T4, or M1b cancer will be excluded
  • Significant comorbid conditions (defined as uncontrolled diabetes, active angina or heart failure, uncontrolled hypertension, 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

  • Shimodaira Y, Slack RS, Harada K, Chen HC, Sagebiel T, Bhutani MS, Lee JH, Weston B, Elimova E, Lin Q, Amlashi FG, Mizrak Kaya D, Blum MA, Roth JA, Swisher SG, Skinner HD, Hofstetter WL, Rogers JE, Mares J, Thomas I, Maru DM, Komaki R, Walsh G, Ajani JA. Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial. Br J Cancer. 2018 Feb 6;118(3):331-337. doi: 10.1038/bjc.2017.423. Epub 2017 Dec 12.

  • Harada K, Wang X, Shimodaira Y, Sagebiel T, Bhutani MS, Lee JH, Weston B, Elimova E, Lin Q, Amlashi FG, Mizrak Kaya D, Lopez A, Blum Murphy MA, Roth JA, Swisher SG, Skinner HD, Hofstetter WL, Rogers JE, Thomas I, Maru DM, Komaki R, Walsh G, Ajani JA. Early Metabolic Change after Induction Chemotherapy Predicts Histologic Response and Prognosis in Patients with Esophageal Cancer: Secondary Analysis of a Randomized Trial. Target Oncol. 2018 Feb;13(1):99-106. doi: 10.1007/s11523-017-0540-3.

  • Ajani JA, Xiao L, Roth JA, Hofstetter WL, Walsh G, Komaki R, Liao Z, Rice DC, Vaporciyan AA, Maru DM, Lee JH, Bhutani MS, Eid A, Yao JC, Phan AP, Halpin A, Suzuki A, Taketa T, Thall PF, Swisher SG. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013 Nov;24(11):2844-9. doi: 10.1093/annonc/mdt339. Epub 2013 Aug 23.

Related Links

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

FluorouracilOxaliplatinRadiotherapySurgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCoordination ComplexesOrganic ChemicalsTherapeutics

Results Point of Contact

Title
Jaffer Ajani, MD / Professor, GI Medical Oncology
Organization
University of Texas (UT) MD Anderson Cancer Center

Study Officials

  • Jaffer Ajani, MD

    UT MD Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 4, 2007

First Posted

September 6, 2007

Study Start

April 1, 2005

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

February 9, 2015

Results First Posted

February 9, 2015

Record last verified: 2015-01

Locations