Heated Intra-peritoneal Chemotherapy with Doxorubicin and Cisplatin for Abdominal for Pelvic Tumors in Pediatric Patients

Early Phase 1

Terminated

• Conditions: Malignant Pelvic Neoplasm; Recurrent Gastric Carcinoma; Recurrent Liposarcoma; Recurrent Ovarian Carcinoma; Recurrent Rhabdomyosarcoma; Refractory Colon Carcinoma; Malignant Abdominal Neoplasm; Refractory Ovarian Carcinoma; Recurrent Colon Carcinoma; Recurrent Desmoplastic Small Round Cell Tumor
• Interventions: Drug: Cisplatin; Procedure: Cytoreductive Surgery; Drug: Doxorubicin; Drug: Hyperthermic Intraperitoneal Chemotherapy; Drug: Sodium Thiosulfate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection

• Registration Number: NCT04213794
• Lead Sponsor: Mayo Clinic

Brief Summary

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.

Detailed 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. 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.

Study Timeline

• Study Start: 2019-11-08
• Study First Submitted: 2019-12-27
• Study First Submitted QC: 2019-12-27
• Study First Posted: 2019-12-30
• Primary Completion: 2024-03-04
• Study Completion: 2024-10-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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:

  • 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (cytoreduction, HIPEC)	Sodium Thiosulfate	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Cisplatin	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Cytoreductive Surgery	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Doxorubicin	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Hyperthermic Intraperitoneal Chemotherapy	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Computed Tomography	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Magnetic Resonance Imaging	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Positron Emission Tomography	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.
Treatment (cytoreduction, HIPEC)	Biospecimen Collection	Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events of cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) in this patient population	Up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Disease-free survival (DFS)	From the time of diagnosis of cancer up to 5 years	Patterns of tumor recurrence and survival will be assessed by reviewing routine surveillance imaging. Patient contact may be contacted by telephone.
Peritoneal-free recurrence	From the time of diagnosis of cancer up to 5 years	Patterns of tumor recurrence and survival will be assessed by reviewing routine surveillance imaging. Patient contact may be contacted by telephone.
Incidence of morbidity	30, 60, and, 90 days post-HIPEC procedure	Will be measured using the Clavien Dindo scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Hospital length of stay	Up to 5 years	Will be tracked using NCI CTCAE version 5.
Operative time	Up to 5 years
Progression free survival (PFS)	From the time protocol treatment is initiated, assessed up to 5 years	The PFS is defined as the time between initiation of protocol treatment and the first occurrence of disease. It will be defined radiologically.
Overall survival (OS)	From the time of diagnosis of cancer up, assessed to 5 years	Will be estimated using the Kaplan-Meier method. Patterns of tumor recurrence and survival will be assessed by reviewing routine surveillance imaging. Patient contact may be contacted by telephone.
Incidence of mortality	30 days post-HIPEC procedure	Will be tracked using NCI CTCAE version 5.
Estimated blood loss (EBL)	Up to 5 years

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States