Bevacizumab With Capecitabine and Oxaliplatin in Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater

This study is currently recruiting participants.
Verified January 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01208103
First received: August 31, 2010
Last updated: January 15, 2014
Last verified: January 2014

August 31, 2010
January 15, 2014
May 2011
May 2015   (final data collection date for primary outcome measure)
Number of Patients with Progression-Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01208103 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Bevacizumab With Capecitabine and Oxaliplatin in Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater
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 goal of this clinical research study is to learn if the combination of capecitabine, oxaliplatin, and bevacizumab can help to control cancer of the small bowel or ampulla of Vater. The safety of this drug combination will also be studied.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Cancers
  • Drug: Capecitabine
    750 mg/m2 by mouth twice a day beginning on day 1-14 of 21 day cycle.
    Other Name: Xeloda
  • Drug: Oxaliplatin
    130 mg/m2 by vein on day 1 over 2 hours of 21 day cycle.
    Other Name: Eloxatin
  • Drug: Bevacizumab
    7.5 mg/kg by vein on day 1 over 90 minutes of 21 day cycle.
    Other Names:
    • Avastin
    • Anti-VEGF monoclonal antibody
    • rhuMab-VEGF
Experimental: Bevacizumab, Capecitabine, Oxaliplatin
Bevacizumab 7.5 mg/kg by vein on day 1 over 90 minutes of 21 day cycle. Capecitabine 750 mg/m2 by mouth twice a day beginning on day 1-14 of 21 day cycle. Oxaliplatin 130 mg/m2 by vein on day 1 over 2 hours of 21 day cycle.
Interventions:
  • Drug: Capecitabine
  • Drug: Oxaliplatin
  • Drug: Bevacizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
Not Provided
May 2015   (final data collection date for primary outcome measure)

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 </= 1.5 x upper limit of normal (ULN)*; AST (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 </= 1.5 x ULN will be used as organ function criteria, 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 </= 1g of protein in 24 hours to be eligible).
  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.
Both
18 Years and older
No
Contact: Michael Overman, MD 713-745-4317
United States
 
NCT01208103
2009-0626
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Genentech
Principal Investigator: Michael Overman, MD UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
January 2014

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