Study of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Brachytherapy for Unresectable or Refractory Pelvic and Abdominal Rhabdomyosarcoma and Undifferentiated Sarcomas in Children

NCT03111069 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2016-0756NCI-2018-01216
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of heated doxorubicin that can be given to patients during surgery with abdominal tumors. The safety of this drug will also be studied.

Conditions

Malignant Neoplasms of Mesothelial and Soft Tissue; Rhabdomyosarcoma, Pelvic; Rhabdomyosarcoma, Abdominal

Keywords

Malignant neoplasms of mesothelial and soft tissue; Pelvic and Abdominal Rhabdomyosarcoma; Undifferentiated Sarcomas; Unresectable or Refractory; Abdominal tumors; Hyperthermic intra-peritoneal chemotherapy; HIPEC; Abdominal surgery; Doxorubicin; Doxorubicin Hydrochloride; Adriamycin PFS; Adriamycin RDF; Adriamycin; Rubex; Intra-operative radiation; IORT; Brachytherapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

  MTD defined as the highest dose in which 1 or fewer patients in 6 treated experience a dose limiting toxicity (DLT). Hematologic DLT defined as Grade IV neutropenia, anemia, or thrombocytopenia per Common Toxicity Criteria. Non-hematologic DLT is any Grade III or IV non-hematologic toxicity excluding Grade III nausea or vomiting, Grade III hepatic toxicity which returns to Grade I within two weeks of the HIPEC, or before hospital discharge, or Grade III fever occurring after the HIPEC per Common Toxicity Criteria.

  1 day

Secondary Outcomes (1)

• Progression of Disease

  6 months

Study Arms (2)

Resectable Intra-Abdominal/Pelvic Tumors

EXPERIMENTAL

Participants receive complete surgical tumor resection with no gross residual disease, followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) using Doxorubicin.

Procedure: Abdominal Surgery; Drug: Doxorubicin

Unresectable Intra-Abdominal/Pelvic Tumors

EXPERIMENTAL

Participants receive debulking surgery followed by intra-operative radiation (IORT) in the form of brachytherapy to the gross residual pelvic tumor sites. Participants have the option of returning for HIPEC 4 weeks (or more) after IORT, if active disease remains.

Procedure: Abdominal Surgery; Radiation: Intra-Operative Radiation

Interventions

Abdominal Surgery PROCEDURE

Resectable Intra-Abdominal/Pelvic Tumors Group: Participants receive peritonectomy, omentectomy, cytoreduction, (complete surgical tumor resection, no gross residual disease). Unresectable Intra-Abdominal/Pelvic Tumors Group: Participants receive debulking surgery (90% resection) , with no more than 5mm thick residual implants, totaling no more than 2.5cm2 of residual tumor.

Resectable Intra-Abdominal/Pelvic Tumors; Unresectable Intra-Abdominal/Pelvic Tumors

Doxorubicin DRUG

Dose Escalation: Heated Doxorubicin delivered by Hyperthermic Intraperitoneal Chemotherapy (HIPEC). After abdominal surgery two large bore catheters are placed in the peritoneal cavity through the incision. Starting dose of Doxorubicin is 15 mg/L of HIPEC perfusate. Dose Expansion Starting Dose: MTD from Dose Escalation.

Also known as: Doxorubicin Hydrochloride, Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex

Resectable Intra-Abdominal/Pelvic Tumors

Intra-Operative Radiation RADIATION

Standard dose brachytherapy delivered to the residual pelvic tumor sites.

Also known as: IORT

Unresectable Intra-Abdominal/Pelvic Tumors

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 1-6 years inclusive
• Histologically proven RMS (with fusion status) or undifferentiated sarcoma of the pelvis or abdomen, group 3 (as defined by the IRS, intergroup rhabdomyosarcoma study group staging system seen in addendum 1)
• Radiologic workup must demonstrate that the disease is confined to the abdominal cavity and/or is not metabolically active on PET (Positron Emission Tomography scan), outside of the abdominal cavity.
• Patients must have a minimum expected duration of survival of greater than 6 weeks as determined and documented by the attending surgeon or medical oncologist.
• 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.
• Patients must have fully intact mental status and normal neurologic abilities. Intact mental status is defined by 'the capacity to identify and recall one's identity and place in time and space. Assessment of mental status and documentation of fully intact mental status by pediatric criteria, will be completed using physical and mental exam by the referring doctor or oncologist.
• Patients must have adequate renal function defined as creatinine clearance or radioisotope GFR (glomerular filtration rate) \>/=70mL/min/1.73m\^2 or a serum creatinine based on age/gender less than the listed value in the table below: 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
• Patients will be eligible if the WBC (white blood cell count) is ≥2000/µl or ANC (absolute neutrophil count) is ≥1,500 and platelets are ≥ 100,000/mm3
• Patients will be eligible if serum total bilirubin and liver enzymes are ≤ 2 times the upper limit of normal
• Patients must be recovered from any toxicity from all prior chemotherapy, immunotherapy, or radiotherapy and be at least 14 days past the date of their last treatment

You may not qualify if:

• Patients will be ineligible if they have any concomitant cardiopulmonary disease which would place them at unacceptable risk for a major surgical procedure
• Patients will be ineligible if they have disease outside of the abdominal cavity which is uncontrolled or PET avid.
• Patients will be ineligible if they have a baseline neurologic toxicity of Grade 3 or greater.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Rhabdomyosarcoma; Abdominal Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Andrea Hayes-Jordan, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 12, 2017
• Study Start: August 1, 2018
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: July 20, 2018

Record last verified: 2018-07