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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00316862
• Other study ID #: CALGB-80302
• Secondary ID: CDR0000468495NCI
• Status: Completed
• Phase: Phase 2
• Start date: February 2006
• Est. completion date: October 15, 2014

Study information

• Verified date: April 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: October 15, 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• cisplatin
Given IV
• irinotecan hydrochloride
Given IV

Procedure:
• therapeutic conventional surgery
Undergo Surgery

Radiation:
• radiation therapy
Undergo radiation

Locations

Country	Name	City	State
United States	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine
United States	Mountainview Medical	Berlin	Vermont
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakes Region General Hospital	Laconia	New Hampshire
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology-Oncology, PC - South Bend	South Bend	Indiana
United States	SUNY Upstate Medical University Hospital	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	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 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	Utility of Early PET Imaging in Predicting Response to Treatment		Up to 55 days
Secondary	Disease-free Survival		Up to 5 years
Secondary	Overall Survival		Up to 5 years
Secondary	Patterns of Failure		Up to 5 years
Secondary	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
Secondary	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