Chemotherapy, Radiation Therapy, and Cetuximab Followed by Surgery, Docetaxel, and Cetuximab in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer

Esophageal Cancer Clinical Trial

Official title:

A Phase II Study to Measure Response Rate and Toxicity of Neo-adjuvant Chemoradiotherapy With Oxaliplatin (OX) and Infusional 5-Fluorouracil (5-FU) Plus Cetuximab Followed by Post-Operative Docetaxel and Cetuximab in Patients With Operable Adenocarcinoma of the Esophagus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00551759
• Other study ID #: CDR0000571857
• Secondary ID: U10CA021115E2205
• Status: Terminated
• Phase: Phase 2
• Start date: October 2, 2008
• Est. completion date: February 2014

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving docetaxel and cetuximab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with cetuximab followed by surgery, docetaxel and cetuximab works in treating patients with esophageal cancer or gastroesophageal junction cancer.

Description:

OBJECTIVES:

Primary

• To determine the pathologic complete response (pCR) rate of neoadjuvant chemoradiotherapy with OX/5-FU/radiotherapy (RT) plus cetuximab in patients with resectable adenocarcinoma of the esophagus.

Secondary

• To evaluate the safety of neoadjuvant chemoradiotherapy with OX/5-FU/RT plus cetuximab in patients with resectable adenocarcinoma of the esophagus.

• To evaluate the safety and tolerability of adjuvant therapy comprising cetuximab and docetaxel in these patients.

• To carry out exploratory studies to determine if activity of this regimen correlates with epidermal growth factor receptor (EGFR)-related genetic and pathway activation markers and circulating endothelial and tumor cells.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemoradiotherapy and cetuximab: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV continuously over 24 hours on days 1-35. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients then proceed to surgery.

• Surgery: Patients undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Patients with an R0 or R1 resection proceed to adjuvant therapy. Patients whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician.

• Adjuvant therapy: Within 4-8 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, and then every 6 months for 3-5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: February 2014
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly diagnosed adenocarcinoma of the esophagus (> 20 cm below the incisors) or gastroesophageal (GE) junction, untreated with chemotherapy, radiation therapy, and surgery. Endoscopy with biopsy and dilation was permitted.

• Tumor stage T2N0M0, T3N0M0, T1-3N+M0, or T1-3N0-1M1A as determined by imaging studies performed no greater than 4 weeks prior to registration, and biopsy, where appropriate. Celiac nodal metastasis (M1A disease) was permitted if other eligibility criteria were met. Data from endoscopic ultrasound and endoscopy were required for staging. The following imaging was required: CT scan with IV contrast and PET or PET+CT. If the PET/CT incorporates CT with IV contrast, then a separate CT is not required. If laparoscopy or other relevant procedures were performed, the data were to be incorporated into stage assignment. Any lesion suspicious for metastasis had to have been biopsied to prove eligibility.

• Tumor extension into cardia, if present, must have been no more than 2 cm.

• Tumors must have been considered surgically resectable (T1-3, not T4).

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Granulocytes > 1,000/ mm³

• Platelets > 100,000 µL

• Creatinine normal or creatinine clearance > 60 mL/min

• Total serum bilirubin < 1.5 mg/dL

• Fertile patients must use effective contraception

• History of a curatively treated malignancy from which the patient has been disease-free for = 2 years and has a survival prognosis of > 5 years

Exclusion Criteria:

• Pregnant or breast-feeding.

• Prior severe infusion reaction to a monoclonal antibody

• prior therapy specifically and directly targeting the epidermal growth factor receptor (EGFR) pathway

• Hypertension

• Uncontrolled diabetes

• Intercurrent illness that would likely interfere with protocol therapy or prevent surgical resection

• Any of the following within the past 6 months:

• New York Heart Association class III-IV congestive heart failure

• Cerebrovascular accident or transient ischemic attack

• Unstable angina or myocardial infarction

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• 5-Fluorouracil
given IV
• Oxaliplatin
given IV
• Cetuximab
given IV
• Docetaxel
given IV

Procedure:
• Surgery
Patients underwent surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab.

Radiation:
• Radiotherapy
Patients underwent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33.

Locations

Country	Name	City	State
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	McFarland Clinic, PC	Ames	Iowa
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Southwest Medical Center	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey
United States	La Grange Oncology Associates - Geneva	Naperville	Illinois
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Pathologic Complete Response	After neoadjuvant therapy, participants underwent surgical resection. The excised tumor was examined by a pathologist. A pathologic complete response is defined as the absence of any histopathologic evidence of tumor in the resected esophageal and nodal tissue specimen.	At time of surgery (which occurred 63 to 91 days after study entry)