Using sirolimus with chemotherapy to treat high-risk solid tumors in children
A Maintenance Protocol of Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors
This study is testing if adding sirolimus to low-dose chemotherapy can help children with high-risk solid tumors live longer without their cancer getting worse after treatment.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 55 (estimated) |
| Ages | 1 Year to 30 Years |
| Sex | All |
| Sponsor | Emory University Academic / other |
| Drugs / interventions | chemotherapy, cyclophosphamide |
| Locations | 5 sites (Atlanta, Georgia and 4 other locations) |
| Trial ID | NCT04469530 on ClinicalTrials.gov |
What this trial studies
This study aims to enhance the two-year progression-free survival rate in children with high-risk solid tumors by administering a maintenance regimen of sirolimus alongside metronomic chemotherapy after standard treatment. Sirolimus, an immunosuppressive drug with anti-tumor properties, will be combined with low-dose daily oral chemotherapy agents like etoposide and cyclophosphamide. The study includes three cohorts: one for patients with high-risk extracranial solid tumors, another for those with recurrent tumors in second complete remission, and a historical control group for comparison. The goal is to evaluate the effectiveness of this combination therapy compared to observation alone.
Who should consider this trial
Good fit: Ideal candidates are children aged 12 months to 30 years with high-risk malignant pediatric extracranial solid tumors in complete remission or with minimal abnormalities post-treatment.
Not a fit: Patients with primary CNS tumors or lymphomas will not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve survival rates for children with high-risk solid tumors.
How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination of sirolimus and metronomic chemotherapy is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion 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.
Exclusion Criteria:
* 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.
Where this trial is running
Atlanta, Georgia and 4 other locations
- Aflac Cancer & Blood Disorders Centers — Atlanta, Georgia, United States (Recruiting)
- Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
- Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC) — Pittsburgh, Pennsylvania, United States (Recruiting)
- Texas Children's Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Kathryn Sutton, MD — Emory University
- Study coordinator: Kathryn Sutton, MD
- Email: Kathryn.Sutton@choa.org
- Phone: 404-785-1651
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.