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Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
cisplatin
irinotecan hydrochloride
proteomic profiling
diagnostic laboratory biomarker analysis
mass spectrometry
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
radiation therapy
Sponsored by
Memorial Sloan Kettering Cancer Center
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, recurrent esophageal cancer, stage III esophageal cancer, stage II esophageal cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction T1, N1, M0 or T2-4, any N, M0 esophageal carcinoma that is surgically resectable Disease must be clinically limited to the esophagus or gastroesophageal junction If tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction No carcinoma in situ (Tis) or tumors determined to be T1, N0 after endoscopy, endoscopic ultrasound, or CT scan No gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus No metastatic disease, including any of the following: M1a celiac or supraclavicular disease Positive malignant cytology of the pleura, pericardium, or peritoneum Radiographic evidence of distant organ involvement, including lung, liver, bone, or brain No involvement of nonregional lymph nodes including supraclavicular or celiac lymph node metastases that cannot be contained within a radiation field No biopsy-proven tumor invasion of the tracheobronchial tree or presence of tracheoesophageal fistula No recurrent laryngeal nerve or phrenic nerve paralysis No CNS or brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL INR ≤ 1.5 (except for patients requiring full-dose warfarin while on bevacizumab) Creatinine ≤ 1.5 mg/dL Bilirubin ≤ 1.5 mg/dL AST and ALT < 2.5 times normal Urine protein ≤ 1+ by urinalysis OR < 1 g of protein by 24-hour urine collection Calcium < 12 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy (except for basal cell or squamous cell carcinoma of the skin, in situ cervical carcinoma, or superficial transitional cell bladder carcinoma) diagnosed and/or treated within the past 3 years No known Gilbert's disease No clinically significant hearing loss No known hypersensitivity to bevacizumab or other study drugs No severe comorbid conditions, including any of the following: Severe uncontrolled diabetes Prior stroke or cerebrovascular disease Uncontrolled infection Nonmalignant illness that precludes study treatment No history of serious systemic disease, including any of the following: Myocardial infarction within the past 6 months Uncontrolled hypertension (i.e., blood pressure > 160/110 mm Hg on medication) Unstable angina New York Heart Association class II-IV congestive heart failure Unstable symptomatic arrhythmia requiring medication Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed Peripheral vascular disease ≥ grade 2 No significant traumatic injury within the past 28 days No evidence of bleeding diathesis or coagulopathy No other concurrent medical or psychiatric condition or disease that would preclude study participation PRIOR CONCURRENT THERAPY: No prior radiotherapy Recovered from prior oncologic or other major surgery No major surgery or open biopsy within the past 28 days No fine-needle aspiration or core biopsies within the past 7 days At least 1 week since prior and no concurrent participation in another experimental drug study (unless Genentech sponsored) No other concurrent major surgery No other concurrent chemotherapy No concurrent sargramostim (GM-CSF) No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, Hypericum perforatum (St. John's wort), or other antiepileptic medication

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

Arm Description

Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 22. Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external beam radiotherapy 5 days a week for 6 weeks beginning on day 43. Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and radiotherapy. Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes every 3 weeks for 6 months

Outcomes

Primary Outcome Measures

Evaluation of Safety and Toxicity
All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v3.0.

Secondary Outcome Measures

Full Information

First Posted
July 19, 2006
Last Updated
April 12, 2016
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00354679
Brief Title
Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer
Official Title
Phase II Trial of Irinotecan, Cisplatin, Bevacizumab and Concurrent Radiotherapy in Locally Advanced Esophageal Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of esophageal cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and monoclonal antibody therapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving irinotecan, cisplatin, and bevacizumab together with radiation therapy followed by surgery and bevacizumab works in treating patients with locally advanced esophageal cancer.
Detailed Description
OBJECTIVES: Primary Evaluate the toxicity and safety of bevacizumab when given together with cisplatin, irinotecan hydrochloride, and radiotherapy followed by surgery and adjuvant bevacizumab in patients with locally advanced esophageal adenocarcinoma. Secondary Observe the rate of pathologic complete response in patients treated with this regimen. Observe overall survival, disease-free survival, and patterns of failure in these patients. Clarify toxicity and tolerability of this regimen. Evaluate pre-treatment levels of vascular endothelial growth factor in patient serum as a corollary of response to this regimen. Correlate serum proteomics data with complete pathologic response. OUTLINE: This is a nonrandomized, open-label study. Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 22. Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external beam radiotherapy 5 days a week for 6 weeks beginning on day 43. Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and radiotherapy. Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes every 3 weeks for 6 months. Blood samples are obtained at baseline, after finishing chemoradiotherapy, and prior to maintenance therapy and are examined by the matrix-assisted laser-desorption ionization time of flight (MALDI-TOF) mass spectometry for proteomic profiling. After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

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, recurrent esophageal cancer, stage III esophageal cancer, stage II 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
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger
Arm Type
Experimental
Arm Description
Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 22. Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external beam radiotherapy 5 days a week for 6 weeks beginning on day 43. Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and radiotherapy. Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes every 3 weeks for 6 months
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Genetic
Intervention Name(s)
proteomic profiling
Intervention Type
Other
Intervention Name(s)
diagnostic laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
mass spectrometry
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Evaluation of Safety and Toxicity
Description
All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v3.0.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction T1, N1, M0 or T2-4, any N, M0 esophageal carcinoma that is surgically resectable Disease must be clinically limited to the esophagus or gastroesophageal junction If tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction No carcinoma in situ (Tis) or tumors determined to be T1, N0 after endoscopy, endoscopic ultrasound, or CT scan No gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus No metastatic disease, including any of the following: M1a celiac or supraclavicular disease Positive malignant cytology of the pleura, pericardium, or peritoneum Radiographic evidence of distant organ involvement, including lung, liver, bone, or brain No involvement of nonregional lymph nodes including supraclavicular or celiac lymph node metastases that cannot be contained within a radiation field No biopsy-proven tumor invasion of the tracheobronchial tree or presence of tracheoesophageal fistula No recurrent laryngeal nerve or phrenic nerve paralysis No CNS or brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL INR ≤ 1.5 (except for patients requiring full-dose warfarin while on bevacizumab) Creatinine ≤ 1.5 mg/dL Bilirubin ≤ 1.5 mg/dL AST and ALT < 2.5 times normal Urine protein ≤ 1+ by urinalysis OR < 1 g of protein by 24-hour urine collection Calcium < 12 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy (except for basal cell or squamous cell carcinoma of the skin, in situ cervical carcinoma, or superficial transitional cell bladder carcinoma) diagnosed and/or treated within the past 3 years No known Gilbert's disease No clinically significant hearing loss No known hypersensitivity to bevacizumab or other study drugs No severe comorbid conditions, including any of the following: Severe uncontrolled diabetes Prior stroke or cerebrovascular disease Uncontrolled infection Nonmalignant illness that precludes study treatment No history of serious systemic disease, including any of the following: Myocardial infarction within the past 6 months Uncontrolled hypertension (i.e., blood pressure > 160/110 mm Hg on medication) Unstable angina New York Heart Association class II-IV congestive heart failure Unstable symptomatic arrhythmia requiring medication Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed Peripheral vascular disease ≥ grade 2 No significant traumatic injury within the past 28 days No evidence of bleeding diathesis or coagulopathy No other concurrent medical or psychiatric condition or disease that would preclude study participation PRIOR CONCURRENT THERAPY: No prior radiotherapy Recovered from prior oncologic or other major surgery No major surgery or open biopsy within the past 28 days No fine-needle aspiration or core biopsies within the past 7 days At least 1 week since prior and no concurrent participation in another experimental drug study (unless Genentech sponsored) No other concurrent major surgery No other concurrent chemotherapy No concurrent sargramostim (GM-CSF) No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, Hypericum perforatum (St. John's wort), or other antiepileptic medication
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
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer

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