Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin for Children With Peritoneal Cancer
Condition: Peritoneal Neoplasms; Retroperitoneal Neoplasms; Gastrointestinal Neoplasms; Adenocarcinoma; Neuroblastoma; Ovarian Neoplasms; Sarcoma; Adrenocortical Carcinoma; Wilms Tumor; Rhabdomyosarcoma; Desmoplastic Small Round Cell Tumor
MeSH terms: Neoplasms; Adenocarcinoma; Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor; Ovarian Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Adrenocortical Carcinoma; Desmoplastic Small Round Cell Tumor; Peritoneal Neoplasms; Retroperitoneal Neoplasms; Hyperthermia; Fever
Study type: Interventional
Phase: Phase 1

Summary: 
      There has been no successful treatment of diffuse peritoneal metastasis or carcinomatosis, in
      childhood tumors. Once this advanced stage of disease is evident, survival is measured in
      weeks. The selective lethal effect of supranormal temperatures on neoplastic cells and the
      additive or synergistic effect of combining chemotherapy has been well established in adult
      clinical trials using continuous hyperthermic peritoneal perfusion (CHPP) for advanced
      peritoneal adenocarcinoma of gastrointestinal origin, ovarian carcinoma and mesothelioma.

      This phase I study will evaluate the safety of continuous hyperthermic peritoneal perfusion
      with escalating doses of intraperitoneal cisplatin in the treatment of children with
      refractory tumors limited to the abdominal cavity. If tumors are outside the abdominal
      cavity, the tumors must be able to be controlled.

      Since CHPP has potential to improve outcome of children with peritoneal and retroperitoneal
      metastases, this study will evaluate the safety of elevated temperature (40oC) with
      intraperitoneal cisplatin chemotherapy.

      Primary Objectives:

        1. To determine the MTD and dose-limiting toxicity of intraperitoneal cisplatin given in
           combination with CHPP as a 90 minute perfusion in children with advanced peritoneal and
           retroperitoneal solid tumors

        2. To determine the safe and tolerable dose of CHPP with cisplatin to be used in Phase II
           trials

        3. To determine the pharmacokinetics of intraperitoneal cisplatin platinum given with CHPP
           as a 90 minute abdominal perfusion (Optional)
    

Detailed description: 
      Cisplatin has an atom at its center that contains platinum. The platinum is supposed to
      poison the cancer cells, causing them to eventually die. Sodium thiosulfate is designed to
      bind-up any Cisplatin that has escaped from the abdomen into the blood stream.

      This is an investigational treatment which has been performed on two children on a
      compassionate use basis in North America. Both surgeries were performed at M.D. Anderson by
      the Study Chairman.

      Before you can start receiving the study drugs, you will have "screening tests." These tests
      will help the doctor decide if you are eligible to take part in this study. A physical exam
      will be performed, and you will have a computed tomography (CT) scan, or magnetic resonance
      imaging (MRI) scan to make sure the disease is only in the abdomen (stomach area). Blood
      (about 1 teaspoon) will be drawn for routine tests. You may have an echocardiogram (ECHO--a
      test to check heart function), and electrocardiogram (ECG--a test to measure electrical
      activity of the heart) if you have ever taken an anthracycline drug. An echocardiogram uses
      sound waves to make pictures of your heart, which helps show how well your heart pumps blood.
      You will be asked to lie on your left side while a technician places a probe with gel on your
      chest to create images of your heart to determine the function and size. Women who are able
      to have children must have a negative urine pregnancy test.

      If you are found to be eligible, you will have a hearing test before your surgery and at your
      one-month evaluation.

      If you are found to be eligible, the abdominal surgery will be performed to try to remove as
      many tumors as possible. 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.

      If the doctor decides that you are eligible to receive the abdominal wash, a drug called
      sodium thiosulfate will be given through a needle in your vein. The abdomen will then be
      temporarily closed. Then the abdominal wash will begin. This will be done in the same room
      while you are under anesthesia. During the "abdominal wash," the heated cisplatin will be
      given into your abdomen and will "wash" over the area of the surgical procedure. There will
      be a pump attached to the plastic tubing and that will pump the drug in and out of your
      abdomen during that 90 minute period while the surgeon is gently compressing your abdominal
      wall so that the drug can reach all areas of your abdomen equally. After 90 minutes the drug
      is removed and your abdomen is 'washed' with saline. Then all the fluid is removed and the
      surgeon permanently closes your abdomen with 3 layers of stitches.

      The actual dose level of cisplatin that you will receive will be decided when you enter the
      study. Participants on this study will be enrolled in groups of 3, and each group will be
      given a specific dose level of cisplatin. The first group will receive the lowest dose of
      cisplatin. If there are no severe or life-threatening side effects in this first group of
      patients, the next group will receive a higher dose of cisplatin and so on. This process of
      increasing the dose level for each new group of participants will continue until some
      patients have severe or life-threatening side effects. At that point, the dose level of
      cisplatin will be lowered and tested again in more participants.

      Blood (about 1 teaspoon) will be drawn for routine tests. This testing will take place during
      the operation and every day until you leave the hospital.

      After you leave the hospital, you will have a study visit about 1 month later, and then every
      3 months for 6 months. At these visits, you will have a CT scan or MRI scan and a physical
      exam to check the status of the disease.

      You will be taken off study if the disease gets worse or if you are disease free at or after
      your 6 month follow-up.

      This is an investigational study. Cisplatin is FDA-approved and commercially available. Up to
      18 patients will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): CHPP of Cisplatin; Abdominal Surgery
Intervention type(s): Drug; Procedure
Intervention description(s): Starting dose of 100 mg/m^2 intraperitoneally delivered as Continuous Hyperthermic Peritoneal Perfusion (CHPP) over 90 minutes at a flow rate of 1.5L/min and a peritoneal temperature of 42.5°Celsius.; Surgical removal of abdominal tumors.
Other intervention name(s): Platinol®-AQ; Platinol®; CDDP; Abdominal Wash; hyperthermic perfusion; cytoreductive surgery
Intervention MeSH terms: Cisplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Children; Pediatric; Peritoneal Tumor; Retroperitoneal Tumor; Gastrointestinal Adenocarcinoma; Desmoplastic Round Cell Tumor; Neuroblastoma; Ovarian Germ Cell; Sarcoma; Adrenocorticocarcinoma; Wilms' Tumor; Rhabdomyosarcoma; Desmoplastic Small Round Cell Tumor; Recurrent Tumors; Cisplatin; Platinol®-AQ; Platinol®; CDDP; Abdominal Wash; Hyperthermic Perfusion; Continuous Hyperthermic Peritoneal Perfusion; CHPP