Phase II Study of Bevacizumab Combined With Capecitabine and Oxaliplatin (CAPOX) in Patients With Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Ampulla of Vater Adenocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Participants With Progression-free Survival (PFS) at Six Months
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This phase II trial studies how well bevacizumab given with capecitabine and oxaliplatin work in treating participants with small bowel or ampulla of Vater adenocarcinoma that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs using in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bevacizumab, capecitabine, and oxaliplatin may work better in treating participants with small intestinal or ampulla of Vater adenocarcinoma.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the progression-free survival (PFS) at six months for patients with advanced adenocarcinoma of the small bowel (small intestine) or ampulla of Vater treated with capecitabine, oxaliplatin (CAPOX) and bevacizumab. SECONDARY OBJECTIVES: I. To determine the response rate (RR) for CAPOX and bevacizumab. II. To determine the overall progression free survival for CAPOX and bevacizumab. III. To determine the overall survival (OS) for CAPOX and bevacizumab. IV. To determine the toxicity of CAPOX and bevacizumab. OUTLINE: Participants receive oxaliplatin via central venous catheter (CVC) over 2 hours and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Participants also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 10 and 30 days, and then every 3 months thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed adenocarcinoma of the small bowel or ampulla of Vater
- •Prior adjuvant chemotherapy (including fluorouracil \[5-FU\], capecitabine, and oxaliplatin) for the treatment of adenocarcinoma of the small bowel or ampulla of Vater is allowed if completed \>= 52 weeks prior to first dose of study treatment
- •Prior capecitabine or 5-FU administered as a radio-sensitizing agent concurrently with external beam radiotherapy is allowed
- •Patients must have metastatic disease
- •A minimum of 4 weeks must have elapsed from completion of any prior chemotherapy or radiotherapy or surgery and the start date of study therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Absolute neutrophil count (ANC) \>= 1,500/ul
- •Platelets \>= 100,000/ul
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN)
- •In patients with known Gilbert's syndrome direct bilirubin =\< 1.5 x ULN will be used as organ function criteria, instead of total bilirubin
Exclusion Criteria
- •Patients who have received prior chemotherapy for their metastatic disease are excluded. Chemotherapy if given as a radiation-sensitizer is allowed
- •Patients may not be receiving any other investigational agents nor have received any investigational drug 28 days prior to enrollment
- •Known history of dihydropyrimidine (DPD) deficiency
- •Peripheral neuropathy of grade 3 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0
- •Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
- •Because of the interaction between coumadin and capecitabine, patients taking therapeutic doses of coumadin-derivative anticoagulants are not eligible. Low-dose coumadin (e.g. 1 mg PO per day) in patients with in-dwelling venous access devices is allowed but increased frequency of international normalized ratio (INR) monitoring is recommended
- •Prior treatment with bevacizumab or known hypersensitivity to any component of bevacizumab
- •Inadequately controlled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \> 90 mmHg)
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Arms & Interventions
Treatment (oxaliplatin, bevacizumab, capecitabine)
Participants receive oxaliplatin via CVC over 2 hours and bevacizumab IV over 30-90 minutes on day 1. Participants also receive capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (oxaliplatin, bevacizumab, capecitabine)
Participants receive oxaliplatin via CVC over 2 hours and bevacizumab IV over 30-90 minutes on day 1. Participants also receive capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Capecitabine
Treatment (oxaliplatin, bevacizumab, capecitabine)
Participants receive oxaliplatin via CVC over 2 hours and bevacizumab IV over 30-90 minutes on day 1. Participants also receive capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Number of Participants With Progression-free Survival (PFS) at Six Months
Time Frame: 6 months
A Bayesian sequential monitoring design will be used. PFS will be estimated using the Kaplan-Meier method.The length of time interval in months from date of first treatment, during and after the treatment a participant lives without progression.
Secondary Outcomes
- To Determine the Overall Survival (OS) for CAPOX and Bevacizumab(39 months)
- To Determine the Response Rate (RR) for CAPOX and Bevacizumab(39 months)
- To Determine the Overall PFS for CAPOX and Bevacizumab(39 months)
- Number of Participants With Adverse Events(39 months)