A Prospective Study of Heated Intra-Peritoneal Chemotherapy (H.I.P.E.C.) With Doxorubicin and Cisplatin in Pediatric Patients With Pelvic and Abdominal Tumors. The TOAST IT Trial (Trial Of Adjuvant Surgical Treatment With Intraperitoneal Chemotherapy)
A Prospective Study of Heated Intra-Peritoneal Chemotherapy (H.I.P.E.C.) With Doxorubicin and Cisplatin in Pediatric Patients With Pelvic and Abdominal Tumors. The TOAST IT Trial (Trial Of Adjuvant Surgical Treatment With Intraperitoneal Chemotherapy)
This early phase I trial studies how well heated intra-peritoneal chemotherapy with doxorubicin and cisplatin work for the treatment of abdominal or pelvic tumors that can be removed by surgery (resectable), does not respond to treatment (refractory), or has come back (recurrent). Heated intra-peritoneal chemotherapy is a procedure performed in combination with abdominal surgery for cancer that has spread to the abdomen. It involves the infusion of a heated chemotherapy solution that circulates into the abdominal cavity. Chemotherapy drugs, such as doxorubicin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Heating a chemotherapy solution and infusing it directly into the abdomen may kill more cells.
PRIMARY OBJECTIVES:
I. To assess the feasibility of heated intra-peritoneal chemotherapy (HIPEC) with doxorubicin (DOXO) and cisplatin (CDDP) after surgical resection of pediatric pelvic and abdominal tumors.
II. To assess morbidity, hospital length of stay and peri-operative mortality outcomes for pediatric patients with intraperitoneal sarcoma undergoing hyperthermic intraperitoneal chemotherapy.
SECONDARY OBJECTIVE:
I. To assess complications and adverse events of HIPEC. II. Evaluate disease recurrence patterns: locoregional versus distant. III. Evaluate disease progression defined by radio-graphically visible nodules greater than 1.5 cm.
OUTLINE:
Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate intravenously (IV) over 12 hours.
After completion of the study treatment, patients are followed every 6 months for 5 years.
Inclusion Criteria:
Patients must have resectable, primary refractory or recurrent intra-abdominal or pelvic tumors based on imaging studies with measurable disease (>= 1 cm in 2 perpendicular planes), or primary tumor with peritoneal implants in whom no known other curative treatment exists, and/or patients not on up-front clinical trial
Evidence of macroscopic or microscopic intra-peritoneal seeding (separate from the primary tumor) identified at the time of exploratory surgery with or without primary tumor resection
Peritoneal cancer index (PCI) =< 20 and surgeons deem high likelihood of complete residual tumor stage R0 (R0) resection
No evidence of distant metastases at the time of enrollment
Histologies to be considered include: rhabdomyosarcoma, liposarcoma, sarcoma (other), ovarian cancer, fallopian tube cancer, gastric cancer, colon cancer, rectal cancer, mesothelioma, and desmoplastic small-round-cell tumor
Patients must be 1-25 years of age at the time of entry into the study
Patients may be included in the study independent of the regimen of previous surgical, radiation, or chemotherapy treatments administered. Given the increased risk of entero-cutaneous fistulae observed in patients treated with HIPEC AFTER radiation therapy, patients will be assessed for risk by radiation oncology
Karnofsky / Lansky performance score of >= 40 or Eastern Cooperative Oncology Group (ECOG) performance score of 3 or less
Platelet count >= 50,000 (independent of transfusion) (performed no later than 14 days before surgery)
Prothrombin and partial thromboplastin times =< 1.2 X normal (performed no later than 14 days before surgery)
Total bilirubin =< 2 X normal (performed no later than 14 days before surgery)
Serum glutamic-oxaloacetic transaminase (SGOT) =< 2 X normal (performed no later than 14 days before surgery)
Serum glutamate pyruvate transaminase (SGPT) =< 2 X normal (performed no later than 14 days before surgery)
Lactate dehydrogenase (LDH) =< 2 X normal (performed no later than 14 days before surgery)
Alkaline phosphatase =< 2 X normal (performed no later than 14 days before surgery)
Neutrophil count >= 750 (performed no later than 14 days before surgery)
Patients must have adequate renal function defined as creatinine clearance (performed no later than 14 days before surgery) or radioisotope GFR (glomerular filtration rate) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender less than the following values:
A signed informed consent form (and assent form when appropriate) approved by the Mayo Clinic (Institutional Review Board [IRB]) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study
Exclusion Criteria:
Females who are pregnant or breast-feeding during the study period will be excluded
Distant metastatic disease not limited to peritoneum:
No critical cumulative dose of previous chemotherapy (total anthracycline dose not >= 435 mg / m^2)
Prior HIPEC within 3 months
Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax > 99.5 Fahrenheit [F]), patients with known immune deficiency disorder or known human immunodeficiency virus infection
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, renal failure, cardiovascular failure, pulmonary failure
Subjects deemed unable to comply with study and/or follow-up procedures
Subjects with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacitation