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

NCT ID: NCT00354679

Last Updated: 2016-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2015-06-30

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan, Cisplatin, Bevacizumab, Radiotherapy, & Surger

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

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

proteomic profiling

Intervention Type: GENETIC

diagnostic laboratory biomarker analysis

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

bevacizumab

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

proteomic profiling

Intervention Type: GENETIC

diagnostic laboratory biomarker analysis

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David H. Ilson, MD, PhD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-06013

Identifier Type: -

Identifier Source: secondary_id

06-013

Identifier Type: -

Identifier Source: org_study_id