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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Gastrointestinal Cancers

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Trial Information

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


The Study Drugs:

Oxaliplatin is designed to block new cancer cells from growing.

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.

Capecitabine is designed to interfere with the growth of cancer cells.

Study Drug Administration:

If you are found eligible to take part in this study, you will receive the study drugs in
21-day "study cycles."

To receive oxaliplatin, you will have a central venous catheter (CVC) placed. A CVC is a
sterile, flexible tube that will be placed into a large vein while you are under local
anesthesia. Your doctor will explain this procedure to you in more detail, and you will be
required to sign a separate consent form for this procedure.

You will receive oxaliplatin through the CVC over 2 hours on Day 1 of each cycle, before
bevacizumab.

You will receive bevacizumab through a needle in your vein on Day 1 of each cycle. The
first time you receive bevacizumab, it will be given over 90 minutes. If you do not have
infusion-related side effects from bevacizumab, all other bevacizumab doses will be given
over 30-60 minutes.

You will take capecitabine by mouth 2 times each day on Days 1-14 of each cycle.
Capecitabine tablets should be taken 12 hours apart, within 30 minutes after eating a meal
with a cup (8 ounces) of water. If you miss a dose, do not try to make up the dose by
doubling your next dose.

Study Visits:

There will be no study visits for Cycle 1. Up to 3 days before or on Day 1 of all Cycles
after Cycle 1, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight, nerve function,
and blood pressure.

- You will be asked about any drugs you may be taking.

- You will be asked about any symptoms or side effects you may be having.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

At the end of Cycles 3, 6, 9, and so on:

- You will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status
of the disease.

- Urine will be collected to check your kidney function. Based on the results of the
urine test, you may be asked to collect your urine over 24 hours to further test your
kidney function. You will be given a container to collect the urine.

Length of Treatment:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
you have intolerable side effects, or if the study is stopped.

End-of-Treatment Visit:

Within 10 days after you stop taking the study drugs, you will have an end-of-treatment
visit. At this visit, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight, nerve function,
and blood pressure.

- You will be asked about any drugs you may be taking.

- You will be asked about any symptoms or side effects you may be having.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status
of the disease.

Follow-Up:

The study staff will ask about any symptoms or side effects you may be having during the 30
days after your last dose of the study drugs. The study staff may contact you by phone or
at the time of a routine clinic visit. If the study staff contacts you by phone, the phone
call should last about 15-30 minutes.

The study staff will also review your medical records and/or contact you to check the status
of the disease every 3 months after you stop receiving the study drugs. If you are contacted
by phone, each phone call should take about 5 minutes.

If you leave the study for any reason other than the disease getting worse, you will have a
CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease every
12 weeks unless you start receiving other treatment or the disease gets worse.

Stopping Study Participation:

You can decide to leave the study at any time. It is important to tell the study doctor if
you are thinking about stopping so any side effects/risks from the treatment can be checked
by your doctor. Another reason to tell your doctor that you are thinking about stopping is
to discuss what follow-up care and testing could be helpful for you.

This is an investigational study. Bevacizumab, oxaliplatin, and capecitabine are each FDA
approved and commercially available for the treatment of some types of cancer, including
colon and rectal cancer. They are not FDA approved for the treatment of small bowel or
ampulla of Vater cancer. The use of the combination of oxaliplatin, capecitabine, and
bevacizumab in patients with cancer of the small bowel or ampulla of Vater is
investigational.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients must have histologically confirmed adenocarcinoma of the small bowel or
ampulla of Vater.

2. Prior adjuvant chemotherapy (including 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.

3. Prior capecitabine or 5-FU administered as a radiosensitizing agent concurrently with
external beam radiotherapy is allowed.

4. Patients must have metastatic disease

5. 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.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

7. Adequate organ function including: Absolute neutrophil count (ANC) >/= 1,500/ul;
platelets >/= 100,000/ul; total bilirubin (SGOT) and ALT (SGPT) < 3 x ULN; calculated creatinine clearance (CrCl) > 50 cc/min
(calculated using the Cockcroft and Gault formula). *In patients with known Gilbert's
syndrome direct bilirubin instead of total bilirubin.

8. 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.

9. 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.

10. 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.

11. (continued from # 8). 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:

1. Patients who have received prior chemotherapy for their metastatic disease are
excluded. Chemotherapy if given as a radiation-sensitizer is allowed.

2. Patients may not be receiving any other investigational agents nor have received any
investigational drug 28 days prior to enrollment.

3. Known history of dihydropyrimidine (DPD) deficiency.

4. Peripheral neuropathy of grade 3 or greater by Common Terminology Criteria for
Adverse Events (CTCAE) 4.0.

5. Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation.

6. Because of the interaction between coumadin and capecitabine, patients taking
therapeutic doses of coumarin-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 INR monitoring is recommended.

7. Prior treatment with bevacizumab or known hypersensitivity to any component of
bevacizumab.

8. Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg
and/or diastolic blood pressure > 90 mmHg).

9. Prior history of hypertensive crisis or hypertensive encephalopathy.

10. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation).

11. New York Heart Association (NYHA) Grade II or greater congestive heart failure.

12. History of myocardial infarction or unstable angina within 6 months prior to Day 1.

13. History of stroke or transient ischemic attack within 6 months prior to Day 1.

14. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Day 1.

15. History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1
month prior to Day 1.

16. History of abdominal fistula or gastrointestinal perforation which must have resolved
at least 6 months prior to Day 1.

17. 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.

18. Core biopsy or other minor surgical procedure excluding placement of a vascular
access device, within 7 days prior to Day 1.

19. Serious, non-healing wound, active ulcer, or untreated bone fracture.

20. 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
21. Known 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 (MRI or CT) during the screening period. Anticonvulsants (stable dose)
are allowed. Treatment for brain metastases may include whole brain radiotherapy
(WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as
deemed appropriate by the treating physician.

22. (continued from # 21) Patients with CNS metastases treated by neurosurgical resection
or brain biopsy performed within 3 months prior to Day 1 will be excluded.

23. Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than this study.

24. Pregnancy (positive pregnancy test) or lactation.

25. Active malignancy, other than superficial basal cell and superficial squamous (skin)
cell, or carcinoma in situ of the cervix, within last five years.

26. Inability to comply with study and/or follow-up procedures.

27. 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.

28. Age <18 years. Because no dosing or adverse event data are currently available on the
use of CAPOX and bevacizumab in patients <18 years of age, children are excluded from
this study.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients with Progression-Free Survival (PFS)

Outcome Time Frame:

6 months

Safety Issue:

Yes

Principal Investigator

Michael Overman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0626

NCT ID:

NCT01208103

Start Date:

May 2011

Completion Date:

Related Keywords:

  • Gastrointestinal Cancers
  • Cancer
  • Small bowel
  • Ampulla of Vater
  • CAPOX Chemotherapy
  • Bevacizumab
  • Capecitabine
  • Oxaliplatin
  • Xeloda
  • Eloxatin
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMab-VEGF
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Gastrointestinal Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030