Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors

NCT ID: NCT02574728

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2026-01-31

Brief Summary

This study aims to determine the efficacy of daily sirolimus and celecoxib, with low dose etoposide alternating with cyclophosphamide for pediatric participants with relapsed or refractory tumors.

Detailed Description

This study aims to learn if the combination of oral sirolimus once daily with celecoxib, and with oral etoposide alternating every 21 days with oral cyclophosphamide (metronomic chemotherapy) is effective in shrinking relapsed or refractory tumors in pediatric participants. In addition, this study seeks to learn the length of time this combination can keep the tumor from growing, learn more about the side effects of sirolimus when used in this combination, and to learn if the sirolimus is working by evaluating blood and tumor tissue.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral sirolimus, celecoxib, etoposide, and cyclophosphamide

Participants in this group will receive oral sirolimus and celecoxib in addition to cycles of oral etoposide and cyclophosphamide for up to two years.

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

The starting dose for sirolimus is 2 mg/m2 once daily. The dose of sirolimus will be individually adjusted to achieve a target serum trough concentration in the range of 10-15 ng/ml. Sirolimus will be given by mouth every day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.

Celecoxib

Intervention Type: DRUG

Celecoxib 100 mg will be given by mouth twice a day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.

Etoposide

Intervention Type: DRUG

Etoposide 50 mg/m2 (maximum dose 100 mg) will be given daily by mouth for the first 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 2.5 mg/Kg (maximum dose 100 mg) will be given daily by mouth for the second 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.

Interventions

Sirolimus

The starting dose for sirolimus is 2 mg/m2 once daily. The dose of sirolimus will be individually adjusted to achieve a target serum trough concentration in the range of 10-15 ng/ml. Sirolimus will be given by mouth every day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.

Intervention Type: DRUG

Celecoxib

Celecoxib 100 mg will be given by mouth twice a day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.

Intervention Type: DRUG

Etoposide

Etoposide 50 mg/m2 (maximum dose 100 mg) will be given daily by mouth for the first 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide 2.5 mg/Kg (maximum dose 100 mg) will be given daily by mouth for the second 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.

Intervention Type: DRUG

Other Intervention Names

Rapamune; rapamycin; Etopophos; Toposar; Cytoxan

Eligibility Criteria

Inclusion Criteria

• Participants with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, and participants with tumors that carry a poor prognosis and have no known standard curative therapy

• Brain tumors of all World Health Organization (WHO) grades, except diffuse intrinsic pontine glioma (DIPG) - enrollment in the brain tumor stratum is closed
• Extracranial solid tumors including histiocytoses
• Participants must have had a histologic verification of malignancy at original diagnosis or relapse, except in participants with optic pathway gliomas, or participants with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta-HCG)
• Tissue blocks or slides must be sent
• Participants must have radiographically measurable disease at the time of study enrollment to be eligible. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as tumor that is measurable (≥ 10 mm) in two perpendicular diameters on MRI and visible on more than one slice. For all patients, tumors that are located in a previously irradiated area may be considered measurable if the lesion has shown tumor growth after radiation or has been biopsied and proven to have active disease.
• Participant's current disease state must be one for which there is no known curative therapy
• Karnofsky performance level of greater than or equal to 50 percent for participants who are greater than 16 years of age at the time of screening
• Lansky performance level of greater than or equal to 50 percent for participants who are less than or equal to 16 years of age at the time of screening
• Fully recovered from acute toxic effects of all prior anti-cancer therapy
• Adequate bone marrow function as deemed by the protocol at the time of screening
• Adequate renal function as deemed by the study protocol at the time of screening
• Adequate liver function as deemed by the study protocol at the time of screening
• Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL
• Random or fasting blood glucose within the upper normal limits for age
• Adequate pulmonary function as deemed by the study protocol at the time of screening

Exclusion Criteria

• Women who are currently pregnant or breastfeeding
• Receiving corticosteroids who have not been on a stable dose for at least 7 days
• Currently receiving enzyme inducing anticonvulsants
• Currently receiving receiving potent CYP3A4 (enzyme) inducers or inhibitors
• Currently receiving another investigational drug
• Currently receiving any other anti-cancer agents
• The use of cannabis oil is prohibited during the first 2 cycles of this protocol. Patients must be off of cannabis oil for 3 days prior to enrollment.
• Uncontrolled infection
• Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cannonball Kids' Cancer Foundation

OTHER

Sponsor Role: collaborator

Hyundai Hope On Wheels

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

William T Cash

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Cash, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Nemours/Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Children's Healthcare of Atlanta-Egleston

Atlanta, Georgia, United States

Children's Healthcare of Atlanta, Scottish Rite

Atlanta, Georgia, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

IRB00082488

Identifier Type: -

Identifier Source: org_study_id