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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00316862
First received: April 19, 2006
Last updated: August 11, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Esophageal Cancer
Drug: cisplatin
Drug: irinotecan hydrochloride
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Preoperative Irinotecan, Cisplatin and Radiation in Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Proportion of patients with adenocarcinoma achieving a pathologic complete response (CR) after surgery [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Utility of early PET imaging in predicting response to treatment [ Time Frame: Up to 55 days ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Patterns of failure [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: February 2006
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, chemoradiotherapy, surgery)

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.

Drug: cisplatin
Given IV
Drug: irinotecan hydrochloride
Given IV
Procedure: therapeutic conventional surgery
Undergo Surgery
Radiation: radiation therapy
Undergo radiation
Other Name: irradiation, radiotherapy, therapy, radiation

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00316862

Locations
United States, Indiana
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Howard Community Hospital
Kokomo, Indiana, United States, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, United States, 46350
Saint Joseph Regional Medical Center
Mishawaka, Indiana, United States, 46545-1470
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
Michiana Hematology-Oncology, PC - South Bend
South Bend, Indiana, United States, 46601
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Maine
CancerCare of Maine at Eastern Maine Medical Center
Bangor, Maine, United States, 04401
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, United States, 04074
United States, Michigan
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Hampshire
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
Concord, New Hampshire, United States, 03301
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
Lakes Region General Hospital
Laconia, New Hampshire, United States, 03246
Elliot Regional Cancer Center at Elliot Hospital
Manchester, New Hampshire, United States, 03103
United States, New York
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: David H. Ilson, MD, PhD Memorial Sloan Kettering Cancer Center
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00316862     History of Changes
Other Study ID Numbers: CALGB-80302  CDR0000468495  NCI-2009-00491  U10CA180821 
Study First Received: April 19, 2006
Last Updated: August 11, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Irinotecan
Cisplatin
Camptothecin
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 23, 2016