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

A Phase II Trial of Preoperative Irinotecan, Cisplatin and Radiation in Esophageal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: irinotecan hydrochloride; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: irradiation, radiotherapy, therapy, radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Up to 5 years
Utility of Early PET Imaging in Predicting Response to Treatment		Up to 55 days
Disease-free Survival		Up to 5 years
Patterns of Failure		Up to 5 years
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	Up to 5 years
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	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2006
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): October 15, 2014

Study Registration Dates

• First Submitted: April 19, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (Estimate): April 21, 2006

Study Record Updates

• Last Update Posted (Actual): May 8, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the esophagus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Cisplatin; Irinotecan
• Other Study ID Numbers: CALGB-80302; U10CA180821 (U.S. NIH Grant/Contract); CDR0000468495 (Registry Identifier: NCI Physician Data Query); NCI-2009-00491 (Registry Identifier: NCI Clinical Trial Reporting Program)