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

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

The goal of this clinical research study is to find the highest tolerated dose of heated intra-abdominal oxaliplatin that can be given to patients with colon cancer. Researchers also want to learn more about the ways that pediatric and young adult colon cancer may be different from colon cancer in adults.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Oxaliplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 </= 2 times 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 </= 3 months.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hyperthermic Intraperitoneal Chemotherapy; After cytoreductive surgery and lysis of adhesions, two large bore catheters are placed in the peritoneal cavity through the incision. Thirty minutes before HIPEC is begun, body temperature is cooled to 35°C. ). The catheters are connected to a perfusion circuit. Heated Oxaliplatin is added to the perfusate administered over 90 minutes. The starting dose of Oxaliplatin is 175 mg/m2.

Drug: Oxaliplatin; Starting dose of Oxaliplatin is 175 mg/m2 delivered by hyperthermic intraperitoneal chemotherapy over 90 minutes.; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerate Dose (MTD) of Oxaliplatin in Hyperthermic Intraperitoneal Chemotherapy	MTD is highest dose in which 1 or fewer patients in 6 treated experience a dose limiting toxicity (DLT). DLT may occur at any time during the initial hospitalization before discharge following the hyperthermic intraperitoneal chemotherapy (HITC). DLT defined in two ways: Hematologic DLT defined as Grade IV neutropenia, anemia, or thrombocytopenia; and Non-hematologic DLT is any Grade III or IV non-hematologic toxicity excluding Grade III nausea or vomiting, Grade III hepatic toxicity which returns to Grade I within two weeks of the HITC, or before hospital discharge, or Grade III fever occurring after the HITC.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Genetic Aberrations in Pediatric Colon Cancer Patients and Adult Patients	Descriptive statistics on genetic aberrations provided, either by tabulations of frequencies or summary statistics including numbers, mean, standard deviation, median, minimum and maximum, when appropriate.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recurrence After HIPEC in Pediatric, Adolescent and Young Adult Age Colon Cancer Patients	Time to recurrence defined as time from treatment to recurrence (event) or to last follow-up date (censored), using the Kaplan-Meier method, with 95% confidence interval. Evaluation of measurable disease by CT or MRI and physical exam.	6 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2014
• Primary Completion (Actual): June 27, 2018
• Study Completion (Actual): June 27, 2018

Study Registration Dates

• First Submitted: February 11, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): July 19, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Adolescent; Colorectal cancer; Pediatric; HIPEC; Colon Cancer; Oxaliplatin; Eloxatin; Hyperthermic Intraperitoneal Chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Body Temperature Changes; Heat Stress Disorders; Colorectal Neoplasms; Hyperthermia; Fever; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: 2013-0438; NCI-2014-01239 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No