RECRUITING

Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors

Conditions

Solid Tumor Pediatrics Chemotherapy Remission Survival

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The primary objective of this study is to improve the 2-year progression-free survival in children with high-risk solid tumors who are administered a maintenance regimen with continuous sirolimus administered on a backbone of metronomic chemotherapy following the completion of "standard" therapy, as compared to high-risk solid tumor patients treated with observation alone following completion of "standard" therapy.

Official Title

A Maintenance Protocol of Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors

Quick Facts

Study Start:2020-09-16

Study Completion:2026-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04469530

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Subjects must be ≥ 12 months and ≤ 30 years of age at the time of study enrollment. * Subjects must have one of the following high-risk malignant pediatric extracranial solid tumors and be in complete remission or have minimal abnormalities on imaging studies after completion of upfront therapy administered with curative intent (cohort 1) or after completion of initial relapse regimen. * Prospective Cohort 1: * Metastatic/unresectable osteosarcoma, metastatic Ewing or Ewing-like sarcoma, high-risk rhabdomyosarcoma, metastatic non-rhabdomyosarcoma soft tissue sarcoma, desmoplastic small round cell tumor (DSRCT), malignant rhabdoid tumor. * Additional high-risk solid tumors at the request of the treating physician after approval by the study chair. * Primary central nervous system (CNS) tumors and lymphomas are not eligible. * Prospective Cohort 2: Recurrent extracranial solid tumor (any histology) in second complete remission following completion of initial relapse regimen. * Subjects must have had histologic verification of malignancy at original diagnosis or relapse. * Subjects must be in complete remission or with minimal radiological abnormalities. Baseline imaging should be the end of therapy imaging obtained at the completion of "standard" upfront therapy (cohort 1) or at the completion of initial relapse regimen (cohort 2). * Karnofsky ≥ 50% for subjects \> 16 years of age and Lansky ≥ 50% for subjects ≤ 16 years of age. * Subjects must have fully recovered from the acute non-hematologic toxic effects of all prior anti-cancer therapy and meet hematologic count parameters. Chronic non-hematologic toxic effects of prior anti-cancer therapy (ie peripheral neuropathy) must be improved to at least grade 2 and be stable or improving on current management. * Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 750/μL and platelet count ≥ 50,000/μL (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to enrollment). * Adequate renal function defined as creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m2 or serum creatinine based on age/gender values derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC). * Adequate liver function defined as: total bilirubin ≤ 2x upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 225 U/L (5x the ULN). * Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL. * Random blood glucose ≤ 1.5x ULN for age. * Adequate pulmonary function defined as normal pulmonary function tests (PFTs), if there is a clinical indication for determination (dyspnea at rest, known requirement for supplemental oxygen). For subjects who do not have respiratory symptoms (no dyspnea at rest, O2 sat ≥ 93% on room air), PFTs are not required.	* Pregnant or breast-feeding women will not be entered on this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. * Concomitant Medication * Subjects receiving corticosteroids must be on a stable or decreasing dose of corticosteroid for the prior 7 days. * Subjects who are currently receiving enzyme inducing anticonvulsants are not eligible. * Subjects must not be receiving potent CYP3A4 inducers or inhibitors. * Subjects who are currently receiving another investigational drug are not eligible. * Subjects who are currently receiving any other anti-cancer agents are not eligible. * Subjects who have an uncontrolled infection are not eligible. * Subjects enrolled on a clinical trial for upfront therapy or relapse therapy for those patients in second complete remission. * Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Inclusion Criteria

Exclusion Criteria

* Subjects must be ≥ 12 months and ≤ 30 years of age at the time of study enrollment.
* Subjects must have one of the following high-risk malignant pediatric extracranial solid tumors and be in complete remission or have minimal abnormalities on imaging studies after completion of upfront therapy administered with curative intent (cohort 1) or after completion of initial relapse regimen.
* Prospective Cohort 1:
* Metastatic/unresectable osteosarcoma, metastatic Ewing or Ewing-like sarcoma, high-risk rhabdomyosarcoma, metastatic non-rhabdomyosarcoma soft tissue sarcoma, desmoplastic small round cell tumor (DSRCT), malignant rhabdoid tumor.
* Additional high-risk solid tumors at the request of the treating physician after approval by the study chair.
* Primary central nervous system (CNS) tumors and lymphomas are not eligible.
* Prospective Cohort 2: Recurrent extracranial solid tumor (any histology) in second complete remission following completion of initial relapse regimen.
* Subjects must have had histologic verification of malignancy at original diagnosis or relapse.
* Subjects must be in complete remission or with minimal radiological abnormalities. Baseline imaging should be the end of therapy imaging obtained at the completion of "standard" upfront therapy (cohort 1) or at the completion of initial relapse regimen (cohort 2).
* Karnofsky ≥ 50% for subjects \> 16 years of age and Lansky ≥ 50% for subjects ≤ 16 years of age.
* Subjects must have fully recovered from the acute non-hematologic toxic effects of all prior anti-cancer therapy and meet hematologic count parameters. Chronic non-hematologic toxic effects of prior anti-cancer therapy (ie peripheral neuropathy) must be improved to at least grade 2 and be stable or improving on current management.
* Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 750/μL and platelet count ≥ 50,000/μL (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to enrollment).
* Adequate renal function defined as creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m2 or serum creatinine based on age/gender values derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).
* Adequate liver function defined as: total bilirubin ≤ 2x upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 225 U/L (5x the ULN).
* Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL.
* Random blood glucose ≤ 1.5x ULN for age.
* Adequate pulmonary function defined as normal pulmonary function tests (PFTs), if there is a clinical indication for determination (dyspnea at rest, known requirement for supplemental oxygen). For subjects who do not have respiratory symptoms (no dyspnea at rest, O2 sat ≥ 93% on room air), PFTs are not required.

* Pregnant or breast-feeding women will not be entered on this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment.
* Concomitant Medication
* Subjects receiving corticosteroids must be on a stable or decreasing dose of corticosteroid for the prior 7 days.
* Subjects who are currently receiving enzyme inducing anticonvulsants are not eligible.
* Subjects must not be receiving potent CYP3A4 inducers or inhibitors.
* Subjects who are currently receiving another investigational drug are not eligible.
* Subjects who are currently receiving any other anti-cancer agents are not eligible.
* Subjects who have an uncontrolled infection are not eligible.
* Subjects enrolled on a clinical trial for upfront therapy or relapse therapy for those patients in second complete remission.
* Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Contacts and Locations

Study Contact

Kathryn Sutton, MD

CONTACT

404-785-1651

Kathryn.Sutton@choa.org

Principal Investigator

Kathryn Sutton, MD

PRINCIPAL_INVESTIGATOR

Emory University

Study Locations (Sites)

Aflac Cancer & Blood Disorders Centers

Atlanta, Georgia, 30322

United States

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15224

United States

Texas Children's Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Emory University

Kathryn Sutton, MD, PRINCIPAL_INVESTIGATOR, Emory University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-09-16

Study Completion Date2026-11

Study Record Updates

Study Start Date2020-09-16

Study Completion Date2026-11

Terms related to this study

Keywords Provided by Researchers

Pediatrics
Chemotherapy
Remission
Survival

Additional Relevant MeSH Terms

Solid Tumor