Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma

Phase II Study of Bevacizumab Combined With Capecitabine and Oxaliplatin (CAPOX) in Patients With Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01208103

Enrollment

Registered

2010-09-23

Start date

2011-05-06

Completion date

2018-03-07

Last updated

2020-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ampulla of Vater Adenocarcinoma, Small Intestinal Adenocarcinoma, Stage IIIA Ampulla of Vater Cancer AJCC v8, Stage III Ampulla of Vater Cancer AJCC v8, Stage IIIA Small Intestinal Adenocarcinoma AJCC v8, Stage IIIB Ampulla of Vater Cancer AJCC v8, Stage IIIB Small Intestinal Adenocarcinoma AJCC v8, Stage III Small Intestinal Adenocarcinoma AJCC v8, Stage IV Ampulla of Vater Cancer AJCC v8, Stage IV Small Intestinal Adenocarcinoma AJCC v8

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.

Interventions

BIOLOGICALBevacizumab

Given IV

DRUGCapecitabine

Given PO

DRUGOxaliplatin

Given CVC

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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 * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 3 x ULN * Calculated creatinine clearance (CrCl) \> 50 cc/min (calculated using the Cockcroft and Gault formula) * Negative serum or urine pregnancy test in women with childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization), within one week prior to initiation of treatment * Patients must sign an Informed Consent and Authorization indicating that they are aware of the investigational nature of this study and the known risks involved * The effects of the combination of CAPOX and bevacizumab on the developing fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation, and for six months following the completion of therapy. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately * Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin or capecitabine or bevacizumab, breast feeding must be discontinued

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) * New York Heart Association (NYHA) grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to day 1 * History of stroke or transient ischemic attack within 6 months prior to day 1. * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1 * History of hemoptysis (\>= 1/2 teaspoon of bright red blood per episode) within 1 month prior to day 1 * History of abdominal fistula or gastrointestinal perforation which must have resolved at least 6 months prior to day 1 * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure excluding placement of a vascular access device, within 7 days prior to day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria at screening as demonstrated by either (1) urine protein:creatinine (UPC) ratio of \>= 1.0 or (2) urine dipstick for proteinuria \>= 2+ (patients discovered to have \>/= 2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must demonstrate =\< 1g of protein in 24 hours to be eligible) * Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician * Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this study * Pregnancy (positive pregnancy test) or lactation * Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix, within last five years * Inability to comply with study and/or follow-up procedures * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit adherence with study requirements

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Progression-free Survival (PFS) at Six Months	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

Measure	Time frame	Description
To Determine the Response Rate (RR) for CAPOX and Bevacizumab	39 months	Complete response + Partial response using RECIST 1.1 (Response Evaluation Criteria in Solid Tumor)
To Determine the Overall PFS for CAPOX and Bevacizumab	39 months	Time interval in months from date of first treatment until the date of first documented progression
To Determine the Overall Survival (OS) for CAPOX and Bevacizumab	39 months	The length of time interval in months from date of first treatment until the date of death or lost follow-up
Number of Participants With Adverse Events	39 months	Toxicity was graded according to the NCI Common terminology Criteria for Adverse Events (CTCAE) 4.0 except for neurosensory and skin toxicity. Neurosensory toxicity was graded according to the Neurologic Toxicity Scale for Oxaliplatin Dose Adjustments.

Countries

United States

Participant flow

Recruitment details

August 2011 to November 2014. All recruitment done at The University of Texas MD Anderson Cancer Center.

Participants by arm

Arm	Count
Bevacizumab + Capecitabine + Oxaliplatin Capecitabine 750 mg/m2 oral twice daily, Days 1 - 14 and Bevacizumab 7.5 mg/kg IV over 90 minutes on Day 1 and Oxaliplatin 130 mg/m2 IV over 2 hours Day 1 of 21-day cycle.	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Bevacizumab + Capecitabine + Oxaliplatin
Age, Continuous	64 years
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants
Race (NIH/OMB) White	22 Participants
Region of Enrollment United States	30 participants
Sex: Female, Male Female	18 Participants
Sex: Female, Male Male	12 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	30 / 30
other Total, other adverse events	30 / 30
serious Total, serious adverse events	4 / 30

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Bevacizumab + Capecitabine + Oxaliplatin	To Determine the Response Rate (RR) for CAPOX and Bevacizumab	Progressive Disease	5 Participants
Bevacizumab + Capecitabine + Oxaliplatin	To Determine the Response Rate (RR) for CAPOX and Bevacizumab	Complete Response	1 Participants
Bevacizumab + Capecitabine + Oxaliplatin	To Determine the Response Rate (RR) for CAPOX and Bevacizumab	Partial Response	13 Participants
Bevacizumab + Capecitabine + Oxaliplatin	To Determine the Response Rate (RR) for CAPOX and Bevacizumab	Stable Disease	10 Participants
Bevacizumab + Capecitabine + Oxaliplatin	To Determine the Response Rate (RR) for CAPOX and Bevacizumab	Unevaluable	1 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026