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

Sponsor
Mayo Clinic (Other)
Overall Status
Recruiting
CT.gov ID
NCT04213794
Collaborator
National Cancer Institute (NCI) (NIH)
43
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1
62.8
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Study Details

Study Description

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:
  1. 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.

  2. To assess morbidity, hospital length of stay and peri-operative mortality outcomes for pediatric patients with intraperitoneal sarcoma undergoing hyperthermic intraperitoneal chemotherapy.

SECONDARY OBJECTIVE:
  1. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
43 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Nov 8, 2019
Anticipated Primary Completion Date :
Jan 30, 2025
Anticipated Study Completion Date :
Jan 30, 2025

Arms and Interventions

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: Cisplatin
Undergo HIPEC with doxorubicin and cisplatin
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
  • Procedure: Cytoreductive Surgery
    Undergo cytoreduction
    Other Names:
  • Cytoreduction
  • Drug: Doxorubicin
    Undergo HIPEC with doxorubicin and cisplatin
    Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin
  • Drug: Hyperthermic Intraperitoneal Chemotherapy
    Undergo HIPEC with doxorubicin and cisplatin
    Other Names:
  • HIPEC
  • Drug: Sodium Thiosulfate
    Given IV
    Other Names:
  • Cyanide Antidote Package
  • Disodium Thiosulfate
  • S-Hydril
  • Sodium Hyposulfate
  • Sodium Thiosulfate Pentahydrate
  • Sodium Thiosulphate
  • Sodothiol
  • Thiosulfate, Sodium, Pentahydrate
  • Thiosulfuric Acid Disodium Salt
  • Outcome Measures

    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]

      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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. Incidence of mortality [30 days post-HIPEC procedure]

      Will be tracked using NCI CTCAE version 5.

    6. Hospital length of stay [Up to 5 years]

      Will be tracked using NCI CTCAE version 5.

    7. Estimated blood loss (EBL) [Up to 5 years]

    8. Operative time [Up to 5 years]

    9. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 25 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Patricio C Gargollo, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT04213794
    Other Study ID Numbers:
    • MC1947
    • NCI-2019-08650
    • MC1947
    • P30CA015083
    First Posted:
    Dec 30, 2019
    Last Update Posted:
    May 13, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    No Results Posted as of May 13, 2022