Escalating Doses of Oxaliplatin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Children and Adolescents With Extensive Colon Carcinoma

Surgery and Study Drug Administration:

If you are found to be eligible to take part in this study, abdominal surgery will be
performed to try to remove as many tumors as possible. The abdominal surgery is not being
performed specifically for this research study and would be performed even if you did not
take part in this study. You will be given a separate consent form to sign that explains the
details and risks of surgery in more detail.

During surgery, the abdomen will be temporarily closed. Then the abdominal wash will begin.
During the "abdominal wash," heated oxaliplatin will be delivered through plastic tubing that
is connected to a pump into the abdomen. The pump pushes the heated oxaliplatin into the
abdomen and then pulls it out and recirculates the oxaliplatin. The skin of the abdomen is
temporarily closed during the abdominal wash. The surgeon will also "wash" over the closed
area of the surgical site. A pump will be used to pump heated oxaliplatin in and out of the
abdomen over 90 minutes while the surgeon gently presses on the abdominal wall so the
oxaliplatin reaches all areas in the abdomen. After 90 minutes, the oxaliplatin is removed
and the abdomen will be "washed" with saline and all fluid will be removed before the surgeon
permanently closes the abdomen with 3 layers of stitches.

Two (2) pea-sized tissue samples (tumor and normal abdominal tissue), 2 tablespoons of blood
will be sent to the laboratory of Dr. Scott Kopetz for tissue evaluation and extraction of
RNA (genetic material). One (1) tumor sample will be removed before the procedure and the
other sample will be removed at the end of the procedure. The samples will be examined under
a microscope and DNA (the genetic material in cells) will be removed to look for any changes
to the DNA. The results of these tests will not be shared with you, nor will they be used for
any decisions regarding your treatment.

There is a chance that the surgeon may decide during the surgery that the abdominal wash will
not be performed, for example if the disease has spread to or attached to certain organs. If
this occurs, your doctor will discuss other treatment options with you.

Study Visits:

On Day 1 after surgery:

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

- You will have a physical exam.

On Days 2-5, 11, 14, and 30 after surgery:

- Blood (about 1-3 teaspoons) will be drawn for routine tests.

- You will have a physical exam.

- On Day 30 only, you will have a hearing test.

If the doctor thinks it is needed, you will also have follow up visits at 3 and 6 months
after surgery. If these visits occur here at MD Anderson, you will not have a hearing test,
but you will have an MRI, CT, or PET-CT scan to check the status of the disease. The 3 and 6
month visits following surgery may be performed at your local doctor's office and/or
laboratory.

Length of Study:

You will remain on study for up to 6 months. You will be taken off study if the disease gets
worse.

If the study doctor learns that the disease has come back or gotten worse at the 6 month
follow-up visit, you may be eligible for a re-perfusion, which is a repeat of the surgery and
study drug administration. If you are eligible for a re-perfusion, your participation on this
study will end and you will be given a new consent form to sign in order to be re-enrolled
back onto this study.

This is an investigational study. Oxaliplatin is FDA approved and commercially available for
the treatment of advanced bladder cancer, metastatic testicular cancer, metastatic ovarian
cancer, hepatoblastoma, neuroblastoma, metastatic appendiceal cancer, and abdominal
mesothelioma. The use of heated oxaliplatin given intra-abdominally in pediatric patients
with colon cancer is investigational. The study doctor can explain how the study drug is
designed to work.

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

Inclusion Criteria:

1. Age 9-21 years.

2. Histologically proven colon carcinoma with serosal invasion or peritoneal disease or a
history of tumor rupture, and/or ascites

3. Radiologic workup must demonstrate that the disease is confined to the abdominal
cavity and/or is controlled outside of the abdominal cavity.

4. Radiologic workup or prior abdominal exploration must be consistent with disease which
can be debulked to a residual size of less than or equal to 1 cm thickness

5. Patients must have a minimum expected duration of survival of greater than 6 weeks as
determined and documented by the attending surgeon or medical oncologist

6. Patients must not have any systemic illness which precludes them from being an
operative candidate as determined by anesthesia preoperative evaluation. This includes
but is not limited to, sepsis, liver failure, pregnant or lactating females.

7. Patients must have fully intact mental status and normal neurologic abilities. Intact
mental status is defined by 'the capacity to identify and recall one's identity and
place in time and space. Assessment of mental status and documentation of fully intact
mental status will be completed using physical and mental exam by the referring doctor
or oncologist.

8. Patients must have Adequate Renal Function Defined as: Creatinine clearance or
radioisotope GFR >/=70ml/min/1.73 m^2 or a serum creatinine based on age/gender less
than listed value in the table below: 1 to < 2 years 0.6 mg/dL for both males and
females, 2 to < 6 years 0.8 mg/dL for both males and females, 6 to < 10 years 1 mg/dL
for both males and females, 10 to < 13 years 1.2 mg/dL for both males and females, 13
to < 16 years 1.5 mg/dL for males and 1.4 mg/dL for females, >/= 16 years 1.7 for
males and 1.4 for females

9. Patients will be eligible if the WBC is >/=2000/µl or ANC is >/=1,500 and platelets
are >/= 100,000/mm3

10. Patients will be eligible if serum total bilirubin and liver enzymes are the upper limit of normal

11. Patients must be recovered from any toxicity from all prior chemotherapy,
immunotherapy, or radiotherapy and be at least 14 days past the date of their last
treatment

Exclusion Criteria:

1. Patients will be ineligible if they have any concomitant cardiopulmonary disease which
would place them at unacceptable risk for a major surgical procedure

2. Patients will be ineligible if they have disease outside of the abdominal cavity which
is uncontrolled

3. Patients will be ineligible if they have a baseline neurologic toxicity of Grade 3 or
greater (because of the potential neurotoxicity associated with platinum)

4. Patients who have failed previous intraperitoneal platinum therapy will be ineligible
("Failed" is having disease recurrence