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Phase II Study of Panitumumab Combined With Capecitabine and Oxaliplatin (CAPOX) in Patients With KRAS Wild-type Locally Advanced or Metastatic Adenocarcinoma of the Small Bowel or Ampulla of Vater


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

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Trial Information

Phase II Study of Panitumumab Combined With Capecitabine and Oxaliplatin (CAPOX) in Patients With KRAS Wild-type Locally Advanced or Metastatic Adenocarcinoma of the Small Bowel or Ampulla of Vater


The Study Drugs:

Panitumumab is designed to "turn off" a protein that is important in cell growth. This may
stop the growth of cancer cells.

Capecitabine is designed to interfere with certain molecules that are important for cell
division, which may cause cancer cells to die.

Oxaliplatin is designed to keep DNA (the genetic material of cells) from making copies of
itself. This may cause cancer cells to die.

Study Drug Administration:

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

On Day 1 of every cycle, you will receive panitumumab by vein over about 60-90 minutes and
oxaliplatin by vein over about 2 hours. These drugs will be given through a central venous
catheter. A central venous catheter 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 take capecitabine by mouth twice a day on Days 1-14 of every cycle. The morning
and evening doses should be taken about 12 hours apart. Take capecitabine with a cup (8
ounces) of water, within 30 minutes after eating a meal. The study staff will tell you how
many tablets you will take. If 1 of the 2 daily doses is higher than the other, you should
take the higher dose in the evening.

Before you are given the dose of oxaliplatin, you may be given aprepitant, ondansetron,
and/or dexamethasone by vein, to lower the risk of nausea and vomiting. You may also take
dexamethasone by mouth on Days 2, 3, and 4.

Study Visits:

On or before Day 1 of each cycle:

- You will have a physical exam, including measurement of your weight.

- You will have a neurosensory assessment.

- Your performance status will be recorded.

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

- Blood (about 2 tablespoons) will be drawn for routine tests.

Every 3 cycles:

- You will have a chest X-ray or a computed tomography (CT) scan of your chest to check
the status of the disease.

- You will have a CT or MRI scan to check the status of the disease. If your scan shows
that you are responding to the treatment, you will have another CT or MRI scan 6 weeks
later.

Length of Study:

You may continue receiving 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
or intolerable side effects occur.

End-of-Treatment:

After you stop taking the study drugs for any reason, you will have an end-of-treatment
visit. The following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight.

- You will have a neurosensory assessment.

- Your performance status will be recorded.

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

- Blood (about 2 tablespoons) will be drawn for routine tests.

- If the doctor thinks it is needed, you will have a CT or MRI scan of the abdomen and
pelvis to check the status of the disease.

Follow-Up:

Thirty (30) days after your last dose of study drug(s), you will be asked about any symptoms
you may be experiencing and any drugs you may be taking. If you are unable to come to MD
Anderson for this, the study staff will call you and ask you these questions. This call
will last about 30 minutes.

You will then be called every 3 months and asked the same questions. Each call will last
about 15-30 minutes.

If you are taken off study treatment for reasons other than the disease getting worse, you
will have a CT or MRI scan of the abdomen and pelvis to check the status of the disease
every 12 weeks (+/- 2 weeks) after the End-of-Treatment visit. This will be done until the
disease gets worse and if you do not start any other anti-cancer treatment.

This is an investigational study. Panitumumab is commercially available and FDA approved to
treat a certain type of colorectal cancer. Capecitabine and oxaliplatin are FDA approved
and commercially available for colon cancer and colorectal cancer. The use of these 3 drugs
in combination is investigational.

Up to 20 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 that is either unresectable or metastatic.

2. Adequate tumor tissue available for KRAS mutational analysis or known KRAS wild-type
status.

3. Prior adjuvant chemotherapy for the treatment of adenocarcinoma of the small bowel or
ampulla of Vater is allowed. If prior adjuvant therapy was a fluoropyrimidine (5-FU
or capecitabine) or platinum agent, then last dose must have been administered =/> 26
weeks prior to first dose of study treatment with the exception that capecitabine or
5-FU administered as a radiosensitizing agent concurrently with external beam
radiotherapy at any time prior to study enrollment is allowed.

4. Patients must have measurable disease as per the revised Response Evaluation Criteria
In Solid Tumors (RECIST) criteria (Version 1.1).

5. If radiation was previously received, the measurable disease must be outside the
previous radiation field, unless this area has demonstrated evidence of radiographic
growth.

6. 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.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

8. Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,500/ul; b)
Platelets =/>100,000/ul; c) Total bilirubin =/< 1.5 x 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; d) AST (SGOT)/ALT (SGPT) < 3 x ULN; e)
Creatinine CrCl > 50 cc/min (Calculated creatinine clearance (CrCl) calculated using
the Cockcroft and Gault formula)

9. Negative urine or serum 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.

10. The effects of the combination of CAPOX and panitumumab 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. 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.

12. Magnesium level =/> lower limit of normal.

Exclusion Criteria:

1. Prior anti-epidermal growth factor receptor antibody therapy (eg. panitumumab or
cetuximab) or prior small molecule anti-epidermal growth factor receptor therapy (eg.
erlotinib) for adenocarcinoma of the small bowel or ampulla of Vater.

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

3. Patients may not be receiving any other investigational agents nor have received any
investigational drug 30 days prior to enrollment.

4. Patients receiving therapeutic anticoagulation, such as Coumadin or low-molecular
weight heparin, for a venous thromboembolism are excluded. Anticoagulation for
reasons other than VTE (atrial fibrillation) is not a cause for exclusion, provided
that patients on Coumadin can be switched to low molecular weight heparin for the
duration of the study. The dose of low molecular weight heparin used will not be a
cause for exclusion.

5. Known history of dihydropyrimidine (DPD) deficiency.

6. Peripheral neuropathy of grade 2 or greater by Common Toxicity Criteria (CTCAE) 4.0.

7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit adherence with
study requirements.

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

9. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung.

10. 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 panitumumab,
breast feeding must be discontinued.

11. 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.

12. Age <18 years. Because no dosing or adverse event data are currently available on the
use of CAPOX and panitumumab 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:

Response Rate (RR) of Patients

Outcome Time Frame:

Response evaluated for up to 6 cycles from first dose; Cycle = 21 days

Safety Issue:

Yes

Principal Investigator

Michael Overman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2009-0458

NCT ID:

NCT01202409

Start Date:

November 2010

Completion Date:

Related Keywords:

  • Gastrointestinal Cancer
  • Ampulla of Vater
  • Adenocarcinoma of the small bowel
  • Metastatic
  • Kirsten rat sarcoma
  • KRAS
  • Capecitabine
  • Xeloda
  • Oxaliplatin
  • Eloxatin
  • CAPOX
  • Panitumumab
  • Vectibix
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Gastrointestinal Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030