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

NCT00354679 | Completed Phase 2 Results

• 3 other identifiers: 06-013P30CA008748MSKCC-06013
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer

Keywords

adenocarcinoma of the esophagus; recurrent esophageal cancer; stage III esophageal cancer; stage II esophageal cancer

Outcome Measures

Primary Outcomes (1)

• Evaluation of Safety and Toxicity

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

  2 years

Study Arms (1)

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

EXPERIMENTAL

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

Biological: bevacizumab; Drug: cisplatin; Drug: irinotecan hydrochloride; Genetic: proteomic profiling; Other: diagnostic laboratory biomarker analysis; Other: mass spectrometry; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

Interventions

bevacizumab BIOLOGICAL

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

cisplatin DRUG

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

irinotecan hydrochloride DRUG

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

proteomic profiling GENETIC

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

diagnostic laboratory biomarker analysis OTHER

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

mass spectrometry OTHER

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

adjuvant therapy PROCEDURE

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

neoadjuvant therapy PROCEDURE

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

therapeutic conventional surgery PROCEDURE

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

radiation therapy RADIATION

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus

Interventions

Bevacizumab; Cisplatin; Irinotecan; Mass Spectrometry; Chemotherapy, Adjuvant; Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Chemistry Techniques, Analytical; Investigative Techniques; Combined Modality Therapy; Therapeutics; Drug Therapy

Results Point of Contact

• Title: Dr. David Ilson
• Organization: Memorial Sloan Kettering Cancer Center

ilsond@mskcc.org

646-888-4183

Study Officials

• David H. Ilson, MD, PhD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2006
• First Posted: July 20, 2006
• Study Start: April 1, 2006
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: May 16, 2016
• Results First Posted: February 12, 2016

Record last verified: 2016-04

Locations

US (1)