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A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Adenocarcinoma of the Esophagus, Adenocarcinoma of the Gastroesophageal Junction, Stage IB Esophageal Cancer, Stage IIA Esophageal Cancer, Stage IIB Esophageal Cancer, Stage IIIA Esophageal Cancer, Stage IIIB Esophageal Cancer

Thank you

Trial Information

A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma


PRIMARY OBJECTIVES:

l. To determine if trastuzumab increases disease-free survival when combined with
trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with
HER2-overexpressing esophageal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate if the addition of trastuzumab to trimodality treatment increases the
pathologic complete response rate and overall survival for patients with HER2-overexpressing
esophageal adenocarcinoma.

II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal
adenocarcinoma.

III. To determine molecular correlates of complete pathologic response, disease-free
survival, and overall survival for patients with HER2-overexpressing esophageal
adenocarcinoma treated with neoadjuvant and maintenance trastuzumab.

IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with
trastuzumab and chemoradiation.

V. To evaluate adverse events associated with the addition of trastuzumab to trimodality
treatment for patients with non-metastatic esophageal adenocarcinoma.

TERTIARY OBJECTIVES:

I. To determine if the addition of trastuzumab to trimodality treatment improves the
patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E)
Esophageal Cancer Subscale (ECS) score.

II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of
neoadjuvant chemoradiation correlates with pathologic complete response.

III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1
year and/or 2 years from the start of chemoradiation.

IV. To determine if the addition of trastuzumab to trimodality treatment improves the
Swallow Index and Eating Index Subscale scores of the FACT-E.

V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation
impacts quality-adjusted survival.

OUTLINE: This is a multicenter study. Patients are stratified according to presence of
adenopathy (yes vs no), and involved celiac nodes (absent vs presence ≤ 2 cm). Patients are
randomized to 1 of 2 treatment arms.

ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also
receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15,
22, 29, and 36 and trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57.
Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes.
Treatment repeats every 21 days for 13 courses in the absence of disease progression or
unacceptable toxicity.

ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also
receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15,
22, 29, and 36.

Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.

Patients may undergo blood and tumor tissue samples collection (during surgery) for
correlative studies and tissue bank. Patients may complete the Functional Assessment of
Cancer Therapy for Esophageal Cancer (FACT-E) and the EuroQol (EQ-5D) questionnaires at
baseline and periodically during study.

After completion of study therapy, patients are followed up every 4 months for 2 years and
then yearly thereafter.


Inclusion Criteria:



- Pathologically confirmed primary adenocarcinoma of the esophagus meeting the
following criteria:

- Involvement of mid (up to 25 cm), distal, or esophagogastric junction

- Involvement of the stomach up to 5 cm allowed

- Patients with tumors at the level of the carina or above must undergo
bronchoscopy to exclude fistula

- Stage T1, N1-2 or T2-3, N0-2 disease by chest, abdominal, or pelvic CT scan or
whole-body PET/CT scan

- No T1,N0 or T4 disease

- No metastatic disease

- Regional adenopathy including para-esophageal, gastric, gastrohepatic, and
celiac (≤ 2 cm) nodes allowed

- No cervical esophageal or proximal esophageal (15-24 cm) carcinoma

- Intent to submit tissue for central HER2 testing

- Must have undergone endoscopy with biopsy

- HER2-overexpressing adenocarcinoma of the esophagus

- Disease must be encompassed in 1 radiotherapy field

- Able to undergo curative resection within 56 days after completion of chemoradiation

- No evidence of tracheoesophageal fistula or invasion into the trachea or major
bronchi

- Zubrod performance status 0-2

- ANC ≥ 1,500 cells/mm³

- Platelet count ≥100,000 cells/mm³

- Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hb ≥ 8.0
g/dL allowed)

- Creatinine ≤ 2 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- AST ≤ 3.0 times ULN

- LVEF normal

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for ≥ 60 days after
completion of chemotherapy or trastuzumab

- No prior invasive malignancy except non-melanomatous skin cancer or curatively
treated carcinoma in situ of the breast, oral cavity, or cervix with no evidence of
disease within the past 2 years

- No medical contraindications to esophagectomy

- No prior allergic reaction to the study drugs involved in this protocol or to a
monoclonal antibody

- No history of congestive heart failure

- No severe or active comorbidity defined as any of the following:

- Unstable angina within the past 6 months

- Transmural myocardial infarction within the past 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics

- AIDS or immunocompromised patients

- HIV testing is not required

- No prior systemic chemotherapy for esophageal cancer

- Prior chemotherapy for a different cancer allowed

- No prior radiotherapy for esophageal cancer or prior chest radiotherapy

- No prior anthracycline or taxane

- No prior therapy with any agent targeting the HER2 pathway or HER1 (EGFR) pathway

- No prior trastuzumab

- No concurrent intensity-modulated radiotherapy

- No other concurrent radiotherapy

- No other concurrent investigational agents

- No other concurrent cytotoxic agents

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival (DFS)

Outcome Description:

DFS will be estimated by the Kaplan-Meier method. The distribution of DFS estimates between the 2 arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with DFS.

Outcome Time Frame:

From the date of randomization to the date of first failure or last follow-up, assessed up to 8 years

Safety Issue:

No

Principal Investigator

Howard Safran

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02601

NCT ID:

NCT01196390

Start Date:

July 2010

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Esophagus
  • Adenocarcinoma of the Gastroesophageal Junction
  • Stage IB Esophageal Cancer
  • Stage IIA Esophageal Cancer
  • Stage IIB Esophageal Cancer
  • Stage IIIA Esophageal Cancer
  • Stage IIIB Esophageal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Esophageal Diseases
  • Esophageal Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Mayo ClinicRochester, Minnesota  55905
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Medical University of South CarolinaCharleston, South Carolina  29425-0721
University of Washington Medical CenterSeattle, Washington  98195-6043
Rhode Island HospitalProvidence, Rhode Island  02903
Porter Adventist HospitalDenver, Colorado  80210
Swedish Medical CenterEnglewood, Colorado  80110
North Suburban Medical CenterThornton, Colorado  80229
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Loyola University Medical CenterMaywood, Illinois  60153
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Northwest Community HospitalArlington Heights, Illinois  60005
Beth Israel Medical CenterNew York, New York  10003
Akron General Medical CenterAkron, Ohio  44302
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
University of Texas Medical BranchGalveston, Texas  77555-1329
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Kansas Medical CenterKansas City, Kansas  66160-7353
Kaiser Permanente Medical Center - Santa ClaraSanta Clara, California  95051-5386
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Medical Center of Central GeorgiaMacon, Georgia  31201
MetroHealth Medical CenterCleveland, Ohio  44109
Central Baptist HospitalLexington, Kentucky  40503
Trinity Cancer Care CenterMinot, North Dakota  58701
Advocate Christ Medical CenterOak Lawn, Illinois  60453
Montefiore Medical CenterBronx, New York  10467-2490
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Rocky Mountain Cancer CenterDenver, Colorado  80218
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Cancer Centers of the CarolinasGreenville, South Carolina  29605
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Sutter Solano Medical CenterVallejo, California  94589
Piedmont HospitalAtlanta, Georgia  30309
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Danville Regional Medical CenterDanville, Virginia  24541
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Mayo Clinic HospitalPhoenix, Arizona  85054-4502
Poudre Valley Radiation OncologyFort Collins, Colorado  80528
Bixby Medical CenterAdrian, Michigan  49221
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Northeast Georgia Medical CenterGainesville, Georgia  30501
Miami Valley HospitalDayton, Ohio  45409
Cancer Treatment CenterWooster, Ohio  44691
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Diagnostic and Treatment CenterWeston, Wisconsin  54476
Singing River HospitalPascagoula, Mississippi  39581
Methodist HospitalHouston, Texas  77030
Martin Memorial Cancer CenterStuart, Florida  34995-9010
Greater Baltimore Medical CenterBaltimore, Maryland  21204
Cancer Centers of the Carolinas - SenecaSeneca, South Carolina  29672
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Memorial Medical CenterSpringfield, Illinois  62781
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Providence HospitalMobile, Alabama  36608
Vanderbilt UniversityNashville, Tennessee  37232-6305
Northwestern UniversityChicago, Illinois  60611
Northwest Cancer SpecialistsVancouver, Washington  98664
Cancer Care Center, IncorporatedSalem, Ohio  44460
University of RochesterRochester, New York  14642
Glens Falls HospitalGlens Falls, New York  12801
Case Western Reserve UniversityCleveland, Ohio  44106
Yale UniversityNew Haven, Connecticut  06520
Emory UniversityAtlanta, Georgia  30322
University of Pittsburgh Medical Center - Shadyside HospitalPittsburgh, Pennsylvania  15213-2582
Providence Portland Medical CenterPortland, Oregon  97213-3635
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
Flower HospitalSylvania, Ohio  43560-2197
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Decatur Memorial HospitalDecatur, Illinois  62526
Lankenau HospitalWynnewood, Pennsylvania  19096
Memorial Health University Medical CenterSavannah, Georgia  31404
University of Southern CaliforniaLos Angeles, California  90033
Rohnert Park Cancer CenterRohnert Park, California  94928
South Sacramento Cancer CenterSacramento, California  95823
University of CincinnatiCincinnati, Ohio  45267-0502
Piedmont Fayette HospitalFayetteville, Georgia  30214
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
Froedtert and the Medical College of WisconsinMilwaukee, Wisconsin  53226
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Saint Joseph's-Candler Health SystemSavannah, Georgia  31405
Saint Francis Hospital and Health CentersBeech Grove, Indiana  46107
McFarland ClinicAmes, Iowa  50010
Mercy HospitalCedar Rapids, Iowa  52403
Ochsner Clinic CCOPNew Orleans, Louisiana  70121
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Saint Louis-Cape Girardeau CCOPSaint Louis, Missouri  63141
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Billings ClinicBillings, Montana  59107-7000
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington CountyMount Holly, New Jersey  08060
Sparta Cancer Treatment CenterSparta, New Jersey  07871
Saint Luke's Roosevelt Hospital Center - Saint Luke's DivisionNew York, New York  10025
Columbia University Medical CenterNew York, New York  10032
Highland HospitalRochester, New York  14620
Kinston Medical Specialists PAKinston, North Carolina  28501
Summa Barberton HospitalBarberton, Ohio  44203
Kettering Medical CenterKettering, Ohio  45429
Saint Charles HospitalOregon, Ohio  43616
North Coast Cancer CareSandusky, Ohio  44870
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
Providence Saint Vincent Medical CenterPortland, Oregon  97225
Salem HospitalSalem, Oregon  97309
Aria Health-Torresdale CampusPhiladelphia, Pennsylvania  19114
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Greenville CCOPGreenville, South Carolina  29615
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Northwest CCOPTacoma, Washington  98405
Wheeling HospitalWheeling, West Virginia  26003
Sacred Heart HospitalEau Claire, Wisconsin  54701
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Saint Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Medical CenterMarinette, Wisconsin  54143
Marshfield Clinic-Minocqua CenterMinocqua, Wisconsin  54548
Marshfield Clinic-Rice Lake CenterRice Lake, Wisconsin  54868
Saint Michael's HospitalStevens Point, Wisconsin  54481
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Northeast Radiation Oncology CenterDunmore, Pennsylvania  18512
Lake University Ireland Cancer CenterMentor, Ohio  44060
University of IllinoisChicago, Illinois  60612
Lahey Clinic Medical CenterBurlington, Massachusetts  01805
Maine Medical Center- Scarborough CampusScarborough, Maine  04074
University of Michigan University HospitalAnn Arbor, Michigan  48109
Renown Regional Medical CenterReno, Nevada  89502
UMDNJ - New Jersey Medical SchoolNewark, New Jersey  07103
Carolinas Medical Center - NortheastConcord, North Carolina  28025
Rex Cancer CenterRaleigh, North Carolina  27607
Cancer Centers of the Carolinas - FarisGreenville, South Carolina  29605
Cancer Centers of the Carolinas-Greer Radiation OncologyGreer, South Carolina  29650
Intermountain Medical CenterMurray, Utah  84157
Dixie Medical Center Regional Cancer CenterSaint George, Utah  84770
Utah Cancer Specialists-Salt Lake CitySalt Lake City, Utah  84106
West Virginia University CharlestonCharleston, West Virginia  25304
Grady Health SystemAtlanta, Georgia  30303
Kaiser Permanente Oakland-BroadwayOakland, California  94611
Kaiser Permanente-Rancho Cordova Cancer CenterRancho Cardova, California  95670
The Permanente Medical Group-Roseville Radiation OncologyRoseville, California  95678
Kaiser Permanente Radiation Oncology Cancer Treatment CenterSanta Clara, California  95051
Kaiser Permanente Cancer Treatment CenterSouth San Francisco, California  94080
Kansas City CCOPPrairie Village, Kansas  66208
Wentworth-Douglass HospitalDover, New Hampshire  03820
UHHS-Chagrin Highlands Medical CenterOrange Village, Ohio  44122
Southern Ohio Medical CenterPortsmouth, Ohio  45662
UHHS-Westlake Medical CenterWestlake, Ohio  44145
Gundersen LutheranLa Crosse, Wisconsin  54601
Robinson Radiation OncologyRavenna, Ohio  44266
Los Angeles County-USC Medical CenterLos Angeles, California  90033
Stanford University Hospitals and ClinicsStanford, California  94305
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
American College of Radiology Imaging NetworkPhiladelphia, Pennsylvania  19103
The Kirklin Clinic at Acton RoadBirmingham, Alabama  35243
Radiation Oncology Associates PCFort Wayne, Indiana  46804
Enloe Medical CenterChico, California  95926
Summa Akron City HospitalAkron, Ohio  44304
William Backus HospitalNorwich, Connecticut  06360
D'Amour Center for Cancer CareSpringfield, Massachusetts  01107
Barnes West County HospitalSaint Louis, Missouri  63141
Siteman Cancer Center - Saint PetersSaint Peters, Missouri  63376
The Cooper Cancer Institute-VoorheesVoorhees, New Jersey  08043
Radiation Oncology Associates IncorporatedProvidence, Rhode Island  02904
Zablocki Veterans Administration Medical CenterMilwaukee, Wisconsin  53295
Door County Cancer CenterSturgeon Bay, Wisconsin  54235-1495
Franciscan St. Francis HealthIndianapolis, Indiana  46237
PeaceHealth Saint Joseph Medical CenterBellingham, Washington  98225
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Memorial Sloan-Kettering Cancer Center at SuffolkCommack, New York  11725
PeaceHealth Southwest Medical CenterVancouver, Washington  98664
IU Health Ball Memorial HospitalMuncie, Indiana  47303
Cape Radiation OncologyCape Girardeau, Missouri  63703
Memorial Sloan Kettering Cancer Center at Basking RidgeBasking Ridge, New Jersey  07920
Memorial Sloan-Kettering Cancer Center Rockville CentreRockville Centre, New York  11570
Memorial Sloan-Kettering Cancer Center at PhelpsSleepy Hollow, New York  10591
Rocky Mountain Cancer Center NorthThornton, Colorado  80221
Comprehensive Cancer Centers of Nevada - Central ValleyLas Vegas, Nevada  89169
Radiation Oncology Centers of Las Vegas - TonopahLas Vegas, Nevada  89106