Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for the Treatment of Resectable, Refractory, or Recurrent Abdominal or Pelvic Tumors in Pediatric Patients, T.O.A.S.T. I.T. Study
Keywords
Abstract
Description
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. Evaluate disease recurrence patterns: locoregional versus distant.
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.
Dates
| Last Verified: | 11/30/2019 |
| First Submitted: | 12/26/2019 |
| Estimated Enrollment Submitted: | 12/26/2019 |
| First Posted: | 12/29/2019 |
| Last Update Submitted: | 05/27/2020 |
| Last Update Posted: | 05/28/2020 |
| Actual Study Start Date: | 11/30/2019 |
| Estimated Primary Completion Date: | 01/29/2025 |
| Estimated Study Completion Date: | 01/29/2025 |
Condition or disease
Intervention/treatment
Drug: Treatment (cytoreduction, HIPEC)
Procedure: Treatment (cytoreduction, HIPEC)
Drug: Treatment (cytoreduction, HIPEC)
Drug: Treatment (cytoreduction, HIPEC)
Drug: Treatment (cytoreduction, HIPEC)
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Treatment (cytoreduction, HIPEC) Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. | Drug: Treatment (cytoreduction, HIPEC) Undergo HIPEC with doxorubicin and cisplatin |
Eligibility Criteria
| Ages Eligible for Study | 1 Year To 1 Year |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | 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 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 may be excluded based on the assessment of risk by our radiation oncology team - 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: - 1 to < 2 years 0.6mg/dL for both males and females - 2 to < 6 years 0.8mg/dL for both males and females - 6 to <10 years 1.0mg/dL for both males and females - 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: - Solid organ metastases (liver, central nervous system, lung) - Known bone marrow involvement - 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 |
Outcome
Primary Outcome Measures
1. Incidence of adverse events of cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) in this patient population [Up to 6 months]
Secondary Outcome Measures
1. Overall survival (OS) [From the time of diagnosis of cancer up, assessed to 5 years]
2. Disease-free survival (DFS) [From the time of diagnosis of cancer up to 5 years]
3. Peritoneal-free recurrence [From the time of diagnosis of cancer up to 5 years]
4. Incidence of morbidity [30, 60, and, 90 days post-HIPEC procedure]
5. Incidence of mortality [30 days post-HIPEC procedure]
6. Hospital length of stay [Up to 5 years]
7. Progression free survival (PFS) [From the time protocol treatment is initiated, assessed up to 5 years]
