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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00551759
Recruitment Status : Terminated (The study used a two-stage design. After stage one, the study was terminated due to excess toxicity.)
First Posted : October 31, 2007
Results First Posted : February 28, 2014
Last Update Posted : November 21, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Brief 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.


Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: 5-Fluorouracil Drug: Oxaliplatin Drug: Cetuximab Drug: Docetaxel Procedure: Surgery Radiation: Radiotherapy Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2008
Actual Primary Completion Date : October 2011
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Neoadjuvant therapy, Surgery, adjuvant therapy

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

Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts 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, pts 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.

Drug: 5-Fluorouracil
given IV
Other Names:
  • 5-FU
  • Fluorouracil
  • Adrucil
  • Efudex

Drug: Oxaliplatin
given IV
Other Names:
  • Trans-l-diaminocyclohexane oxalatoplatinum
  • Cis-[oxalato (trans-I-1,2-diaminocyclohexane) platinum(II)]
  • l-OHP
  • Eloxatin
  • Eloxatine
  • Dacplat
  • 5R96669

Drug: Cetuximab
given IV
Other Names:
  • Erbitux
  • C225

Drug: Docetaxel
given IV
Other Names:
  • Taxotere
  • RP 56976

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.




Primary Outcome Measures :
  1. Proportion of Patients With Pathologic Complete Response [ Time Frame: At time of surgery (which occurred 63 to 91 days after study entry) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00551759


Locations
Show Show 109 study locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Michael K. Gibson, MD University of Pittsburgh

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Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00551759    
Other Study ID Numbers: CDR0000571857
U10CA021115 ( U.S. NIH Grant/Contract )
E2205 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
First Posted: October 31, 2007    Key Record Dates
Results First Posted: February 28, 2014
Last Update Posted: November 21, 2017
Last Verified: October 2017
Keywords provided by Eastern Cooperative Oncology Group:
adenocarcinoma of the esophagus
chemoradiotherapy
oxaliplatin
cetuximab
docetaxel
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Docetaxel
Oxaliplatin
Fluorouracil
Cetuximab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological