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Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cisplatin
irinotecan hydrochloride
therapeutic conventional surgery
radiation therapy
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer

Eligibility Criteria

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

Histologically or cytologically confirmed adenocarcinoma, poorly differentiated carcinoma, or carcinoma not otherwise specified, of the esophagus or gastroesophageal junction; biopsy or cytology of the primary tumor, or of involved regional lymph nodes, is acceptable Tumors must be TNM stage T2-4, N0-1, M0 as determined by pretreatment endoscopic ultrasound; T1 tumors are eligible if they are T1, N1, M0; regional thoracic lymph node involvement (N1) is permitted Disease must be clinically limited to the esophagus or gastroesophageal junction; if the tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction; adenocarcinomas of the distal esophagus would therefore include tumors of the distal esophagus, or Siewert type I according to the Siewert classification, and tumors of the gastroesophageal junction which involve equally both the distal esophagus and proximal stomach, or Siewert type II; tumor must be surgically resectable No TIS (in-situ carcinoma) and tumors determined to be T1N0 following endoscopic ultrasound No clinical involvement on endoscopic ultrasound (EUS), computed tomography (CT) scan, or PET scan of supraclavicular or celiac lymph node involvement (stage IVa, T any N any M1a) unless this is proven to be a false positive by an appropriate biopsy No patients with cervical esophageal tumors, or gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus No patients with tracheoesophageal fistulas Patients with evidence of metastatic disease are not eligible; this includes: Positive malignant cytology of the pleura, pericardium or peritoneum Radiographic evidence of distance organ involvement including lung, liver, bone, or brain No prior chemotherapy or radiotherapy is permitted; patients must be at least 4 weeks since major surgery, or must have recovered from the effects of minor surgery (laparoscopy, thoracoscopy) No prior malignancies (other than basal cell/squamous carcinoma of the skin, in-situ cervical carcinoma, or superficial transitional cell bladder carcinoma) are permitted unless diagnosed and/or treated >= 3 years before registration and without evidence of recurrence Eastern Cooperative Oncology Group (ECOG) performance status 0-1 No evidence of recurrent laryngeal nerve or phrenic nerve paralysis No known Gilbert's disease No clinically significant hearing loss; audiograms should be done in patients in which they are clinically indicated No history of active seizure disorder; no ongoing treatment with phenytoin, phenobarbital, or other antiepileptic medication; patients who are receiving valproic acid are eligible No New York Heart Association class III or IV heart disease; no angina or myocardial infarction within the last 6 months Inclusion Criteria: No history of clinically significant ventricular arrhythmia requiring ongoing medication with antiarrhythmics Absolute neutrophil count (ANC) >= 1,500/ul Platelet count >= 100,000/ul Hemoglobin >= 9 gm/dl Serum creatinine =< upper limit of normal (ULN) Total serum bilirubin =< 1.5 mg/dl Forced expiratory volume in 1 second (FEV-1) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size Pulmonary function tests (PFT) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size

Sites / Locations

  • Elkhart General Hospital
  • Howard Community Hospital
  • Center for Cancer Therapy at LaPorte Hospital and Health Services
  • Saint Joseph Regional Medical Center
  • CCOP - Northern Indiana CR Consortium
  • Memorial Hospital of South Bend
  • Michiana Hematology-Oncology, PC - South Bend
  • Holden Comprehensive Cancer Center at University of Iowa
  • CancerCare of Maine at Eastern Maine Medical Center
  • Maine Center for Cancer Medicine and Blood Disorders - Scarborough
  • Lakeland Regional Cancer Care Center - St. Joseph
  • Methodist Estabrook Cancer Center
  • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
  • New Hampshire Oncology - Hematology, PA - Hooksett
  • Lakes Region General Hospital
  • Elliot Regional Cancer Center at Elliot Hospital
  • Veterans Affairs Medical Center - Buffalo
  • Roswell Park Cancer Institute
  • Memorial Sloan-Kettering Cancer Center
  • SUNY Upstate Medical University Hospital
  • Wayne Memorial Hospital, Incorporated
  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
  • Mountainview Medical
  • Fletcher Allen Health Care - University Health Center Campus

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, chemoradiotherapy, surgery)

Arm Description

INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.

Outcomes

Primary Outcome Measures

Proportion of Patients With Adenocarcinoma Achieving a Pathologic Complete Response (CR) After Surgery
A pathological complete response is defined as no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor

Secondary Outcome Measures

Utility of Early PET Imaging in Predicting Response to Treatment
Disease-free Survival
Overall Survival
Patterns of Failure
Proportion of Patients Experiencing Grade 3 or Greater Pneumonitis or Esophagitis
Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis, deemed at least possibly related to treatment graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Proportion of Patients Experiencing Grade 3 or Greater Hematologic and Non-hematologic Toxicity
Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, deemed as at least possibly related to treatment, graded using the NCI CTCAE version 3.0

Full Information

First Posted
April 19, 2006
Last Updated
April 9, 2018
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00316862
Brief Title
Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery
Official Title
A Phase II Trial of Preoperative Irinotecan, Cisplatin and Radiation in Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
February 2006 (Actual)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
October 15, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies how well giving cisplatin and irinotecan hydrochloride together with radiation therapy works in treating patients with esophageal cancer or gastroesophageal junction cancer that can be removed by surgery. Drugs used in chemotherapy, such as cisplatin and irinotecan hydrochloride, 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. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the pathologic complete response rate in patients with surgically resectable esophageal cancer treated pre-operatively with induction chemotherapy with weekly cisplatin and irinotecan (irinotecan hydrochloride) followed by concurrent cisplatin/irinotecan and radiation therapy. SECONDARY OBJECTIVES: I. To evaluate potential response or progression of disease during induction chemotherapy with positron emission tomography (PET) scan. II. To evaluate the toxicity and tolerability of therapy, including surgical morbidity and mortality. III. To determine the overall survival, disease free survival, and pattern of failure. OUTLINE: INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, chemoradiotherapy, surgery)
Arm Type
Experimental
Arm Description
INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo Surgery
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiation
Primary Outcome Measure Information:
Title
Proportion of Patients With Adenocarcinoma Achieving a Pathologic Complete Response (CR) After Surgery
Description
A pathological complete response is defined as no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Utility of Early PET Imaging in Predicting Response to Treatment
Time Frame
Up to 55 days
Title
Disease-free Survival
Time Frame
Up to 5 years
Title
Overall Survival
Time Frame
Up to 5 years
Title
Patterns of Failure
Time Frame
Up to 5 years
Title
Proportion of Patients Experiencing Grade 3 or Greater Pneumonitis or Esophagitis
Description
Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis, deemed at least possibly related to treatment graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame
Up to 5 years
Title
Proportion of Patients Experiencing Grade 3 or Greater Hematologic and Non-hematologic Toxicity
Description
Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, deemed as at least possibly related to treatment, graded using the NCI CTCAE version 3.0
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Histologically or cytologically confirmed adenocarcinoma, poorly differentiated carcinoma, or carcinoma not otherwise specified, of the esophagus or gastroesophageal junction; biopsy or cytology of the primary tumor, or of involved regional lymph nodes, is acceptable Tumors must be TNM stage T2-4, N0-1, M0 as determined by pretreatment endoscopic ultrasound; T1 tumors are eligible if they are T1, N1, M0; regional thoracic lymph node involvement (N1) is permitted Disease must be clinically limited to the esophagus or gastroesophageal junction; if the tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction; adenocarcinomas of the distal esophagus would therefore include tumors of the distal esophagus, or Siewert type I according to the Siewert classification, and tumors of the gastroesophageal junction which involve equally both the distal esophagus and proximal stomach, or Siewert type II; tumor must be surgically resectable No TIS (in-situ carcinoma) and tumors determined to be T1N0 following endoscopic ultrasound No clinical involvement on endoscopic ultrasound (EUS), computed tomography (CT) scan, or PET scan of supraclavicular or celiac lymph node involvement (stage IVa, T any N any M1a) unless this is proven to be a false positive by an appropriate biopsy No patients with cervical esophageal tumors, or gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus No patients with tracheoesophageal fistulas Patients with evidence of metastatic disease are not eligible; this includes: Positive malignant cytology of the pleura, pericardium or peritoneum Radiographic evidence of distance organ involvement including lung, liver, bone, or brain No prior chemotherapy or radiotherapy is permitted; patients must be at least 4 weeks since major surgery, or must have recovered from the effects of minor surgery (laparoscopy, thoracoscopy) No prior malignancies (other than basal cell/squamous carcinoma of the skin, in-situ cervical carcinoma, or superficial transitional cell bladder carcinoma) are permitted unless diagnosed and/or treated >= 3 years before registration and without evidence of recurrence Eastern Cooperative Oncology Group (ECOG) performance status 0-1 No evidence of recurrent laryngeal nerve or phrenic nerve paralysis No known Gilbert's disease No clinically significant hearing loss; audiograms should be done in patients in which they are clinically indicated No history of active seizure disorder; no ongoing treatment with phenytoin, phenobarbital, or other antiepileptic medication; patients who are receiving valproic acid are eligible No New York Heart Association class III or IV heart disease; no angina or myocardial infarction within the last 6 months Inclusion Criteria: No history of clinically significant ventricular arrhythmia requiring ongoing medication with antiarrhythmics Absolute neutrophil count (ANC) >= 1,500/ul Platelet count >= 100,000/ul Hemoglobin >= 9 gm/dl Serum creatinine =< upper limit of normal (ULN) Total serum bilirubin =< 1.5 mg/dl Forced expiratory volume in 1 second (FEV-1) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size Pulmonary function tests (PFT) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David H. Ilson, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Elkhart General Hospital
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46515
Country
United States
Facility Name
Howard Community Hospital
City
Kokomo
State/Province
Indiana
ZIP/Postal Code
46904
Country
United States
Facility Name
Center for Cancer Therapy at LaPorte Hospital and Health Services
City
La Porte
State/Province
Indiana
ZIP/Postal Code
46350
Country
United States
Facility Name
Saint Joseph Regional Medical Center
City
Mishawaka
State/Province
Indiana
ZIP/Postal Code
46545-1470
Country
United States
Facility Name
CCOP - Northern Indiana CR Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Memorial Hospital of South Bend
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Michiana Hematology-Oncology, PC - South Bend
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Holden Comprehensive Cancer Center at University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1002
Country
United States
Facility Name
CancerCare of Maine at Eastern Maine Medical Center
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Facility Name
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Lakeland Regional Cancer Care Center - St. Joseph
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
Methodist Estabrook Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
City
Concord
State/Province
New Hampshire
ZIP/Postal Code
03301
Country
United States
Facility Name
New Hampshire Oncology - Hematology, PA - Hooksett
City
Hooksett
State/Province
New Hampshire
ZIP/Postal Code
03106
Country
United States
Facility Name
Lakes Region General Hospital
City
Laconia
State/Province
New Hampshire
ZIP/Postal Code
03246
Country
United States
Facility Name
Elliot Regional Cancer Center at Elliot Hospital
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03103
Country
United States
Facility Name
Veterans Affairs Medical Center - Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
SUNY Upstate Medical University Hospital
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Wayne Memorial Hospital, Incorporated
City
Goldsboro
State/Province
North Carolina
ZIP/Postal Code
27534
Country
United States
Facility Name
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
Facility Name
Mountainview Medical
City
Berlin
State/Province
Vermont
ZIP/Postal Code
05602
Country
United States
Facility Name
Fletcher Allen Health Care - University Health Center Campus
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

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