A Multicenter, Open-Label, Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
A Multicenter, Open-Label, Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
This phase II trial is studying how well giving irinotecan and cisplatin together with bevacizumab works in treating patients with unresectable or metastatic gastric (stomach) or gastroesophageal junction adenocarcinoma (cancer). Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the efficacy of irinotecan, cisplatin, and bevacizumab, in terms of time to progression, in patients with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
SECONDARY OBJECTIVES:
I. Determine other measures of efficacy, including response rate and median and 1-year survival, in patients treated with this regimen.
II. Determine the toxicity of this regimen in these patients. III. Correlate CT perfusion imaging results with the efficacy of this regimen, in terms of time to progression, objective response, and survival, in these patients.
IV. Determine the feasibility of serial serum proteomic assays in predicting response to therapy, in terms of time to progression, objective response, and survival, in patients treated with this regimen.
V. To bank paraffin stored tumor biopsy material for future planned immunohistochemistry studies to correlate with sensitivity to bevacizumab based combination chemotherapy.
OUTLINE: This is an open-label, non-randomized, multicenter study.
Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year.
Inclusion Criteria:
Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma
No ulcerated, non-healing tumors or tumors that have developed a malignant fistula
No esophageal tumors
No known or active brain metastases
Performance status - Karnofsky 60-100%
Performance status - ECOG 0-2
Neutrophil count >= 1,500/mm^3
Platelet count >= 75,000/mm^3
No bleeding diathesis or coagulopathy
Bilirubin =< 1.5 mg/dL
AST and ALT =< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
PT (INR) =< 1.5
PTT =< 3 seconds above ULN
Creatinine =< 1.5 mg/dL
Proteinuria < 1+
Protein < 500 mg/24-hour urine collection
No acute ischemia or significant conduction abnormality by EKG
No clinically significant cardiovascular disease
No uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)
No myocardial infarction within the past 6 months
No unstable angina within the past 6 months
No transient ischemic attack within the past 6 months
No cerebrovascular accident within the past 6 months
No other arterial thromboembolic event within the past 6 months
No New York Heart Association class II-IV congestive heart failure
No serious cardiac dysrhythmia requiring medication
No peripheral vascular disease (grade II or greater)
No history of stroke
No CNS disease within the past 5 years (e.g., uncontrolled seizures)
No other concurrent uncontrolled illness
No ongoing or active infection requiring parental antibiotics on Day 0 of study
No serious, non-healing wound
No serious wound healing by secondary intention
No ulcer
No bone fracture
No psychiatric illness or social situation that would preclude study compliance
No significant traumatic injury within the past 28 days
No other neoplastic disease within the past 3 years except basal cell skin cancer, carcinoma in situ of the cervix, or nonmetastatic prostate cancer
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
No other medical condition that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 months after study participation
More than 8 weeks since prior immunotherapy and recovered
No other concurrent biologic or immunologic agents
No other concurrent bevacizumab
No prior chemotherapy for metastatic disease
No prior cisplatin or irinotecan
Prior neoadjuvant and/or adjuvant chemotherapy or chemoradiotherapy allowed
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No other concurrent chemotherapy
More than 3 weeks since prior radiotherapy and recovered
No concurrent radiotherapy
More than 28 days since prior major surgical procedure or open biopsy
More than 7 days since prior fine needle aspirations or core biopsies
No concurrent major surgery
No other concurrent investigational agents
No other concurrent anticancer therapy
No concurrent chronic daily aspirin (> 325 mg/day)
No concurrent nonsteroidal anti-inflammatory medications that would inhibit platelet function at doses used to treat chronic inflammatory diseases
Full-dose anticoagulants allowed, provided the following criteria are met:
No concurrent thrombolytic agents
No concurrent vitamins, antioxidants, herbal preparations, or supplements