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

NCT04469530 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00000113
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Solid Tumor

Keywords

Pediatrics; Chemotherapy; Remission; Survival

Outcome Measures

Primary Outcomes (1)

• Two-year progression-free survival in patients with high-risk solid tumors

  Two-year progression-free survival in patients with high-risk solid tumors who complete a 12- month course of maintenance chemotherapy with daily sirolimus and twice daily celecoxib on a backbone of low-dose oral metronomic chemotherapy following completion of "standard" therapy as compared to a historical cohort of matched patients treated with observation only following completion of "standard" therapy.

  up to 2 years

Secondary Outcomes (6)

• Median progression-free survival of children with high-risk solid tumors

  up to 2 years

• Two-year progression-free survival for all prospectively enrolled participants

  up to 2 years

• Two-year overall survival for all prospectively enrolled participants

  up to 2 years

• Number of cases of severe toxicities

  up to 2 years

• Number of patients who come off protocol therapy due to toxicity or non-compliance

  up to 2 years

Study Arms (2)

Maintenance Chemotherapy Regimen

EXPERIMENTAL

Participants with metastatic osteosarcoma, metastatic Ewing sarcoma, high-risk rhabdomyosarcoma, metastatic non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), desmoplastic small round cell tumor (DSRCT), and malignant rhabdoid tumor (MRT) in first complete remission (cohort 1) or participants with recurrent solid tumors (any histology) in second complete remission (cohort 2), receiving a maintenance chemotherapy regimen administered as a 12-month course of continuous sirolimus with celecoxib and low-dose oral etoposide alternating every 21 days with low-dose oral cyclophosphamide following the completion of "standard" therapy.

Drug: Sirolimus; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Celecoxib

Historical Control Cohort Receiving Standard Therapy

NO INTERVENTION

This study arm is a historical control cohort of patients matched with cohort 1 on diagnosis, age, metastatic site, and date of diagnosis. The matched historical controls will be obtained from the same treating institution as the corresponding case to account for institutional differences in treatment and supportive care. Patients in the historical control cohort received standard therapy.

Interventions

Sirolimus DRUG

Sirolimus is given at a dose of 2 mg/m2 once daily. The amber oral dose syringe should be used to withdraw the prescribed amount of sirolimus oral solution from the bottle. The solution can be drunk or administered at once to assure delivery of all of the medication. It is safe for administration through a nasogastric or G-tube. For tablets, the tablet should not be crushed, split, or otherwise altered. As with the liquid dosing form, the tablets should be given within two hours each day and should be at consistent intervals with regard to meals.

Also known as: Rapamune, rapamycin

Maintenance Chemotherapy Regimen

Cyclophosphamide DRUG

A synthetic antineoplastic drug chemically related to the nitrogen mustards. The drug is administered orally daily, in the formulation appropriate for age. The solution should be diluted in 20-30 ml of appropriate liquid before administration through nasogastric (NG) tube or gastrostomy (G) tube, with adequate flushing after administration to prevent obstruction of the feeding tube.

Also known as: Cytoxan

Maintenance Chemotherapy Regimen

Etoposide DRUG

A semisynthetic derivative of podophyllotoxin which functions as mitotic inhibitor but does not interfere with microtubular assembly. The drug is administered orally daily, in the formulation appropriate for age.

Also known as: VP-16, VePesid, Toposar, Etopophos

Maintenance Chemotherapy Regimen

Celecoxib DRUG

The drug is administered orally daily, in the formulation appropriate for age.The solution is safe for administration through a nasogastric or G-tube.

Also known as: Celebrex

Maintenance Chemotherapy Regimen

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• PeachBowl LegACy Fund: collaborator

Study Sites (5)

Aflac Cancer & Blood Disorders Centers

Atlanta, Georgia, 30329, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

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

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Texas Children's Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Interventions

Sirolimus; Cyclophosphamide; Etoposide; etoposide phosphate; Celecoxib

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kathryn Sutton, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathryn Sutton, MD

CONTACT

404-785-1651; Kathryn.Sutton@choa.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Three cohorts of patients will be treated: 1) common solid tumors in complete remission, 2) common solid tumors in second complete remission, and 3) historical control cohort of patients derived from the electronic medical record matched with same diagnosis, metastatic site, and date of diagnosis utilizing a 2:1 ratio
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 14, 2020
• Study Start: September 16, 2020
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available for sharing after data analysis for this study is completed.
• Access Criteria: Data will be available for sharing upon request.

Locations

US (5)