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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00354679
First received: July 19, 2006
Last updated: March 13, 2014
Last verified: March 2014

July 19, 2006
March 13, 2014
April 2006
April 2015   (final data collection date for primary outcome measure)
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00354679 on ClinicalTrials.gov Archive Site
  • Rate of pathologic complete response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pattern of failure [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pre-treatment levels of vascular endothelial growth factor as a corollary of response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlation of serum proteomics data with complete pathologic response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer
Phase II Trial of Irinotecan, Cisplatin, Bevacizumab and Concurrent Radiotherapy in Locally Advanced Esophageal Adenocarcinoma

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Esophageal Cancer
  • 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
Experimental: 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

Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
33
April 2015
April 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00354679
06-013, P30CA008748, MSKCC-06013
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Study Chair: David H. Ilson, MD, PhD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP