Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

Summary

This is a Phase I trial with new experimental drugs such as simvastatin in combination with topotecan and cyclophosphamide in the hopes of finding a drug that may work against tumors that have come back or that have not responded to standard therapy. This study will define toxicity of high dose simvastatin in combination with topotecan and cyclophosphamide and evaluate for cholesterol levels and IL6/STAT3 pathway changes as biomarkers of patient response.

Conditions

• Retinoblastoma
• Clear Cell Sarcoma
• Renal Cell Carcinoma
• Rhabdoid Tumor
• Wilms Tumor
• Hepatoblastoma
• Neuroblastoma
• Germ Cell Tumors
• Ewings Sarcoma
• Non-rhabdomyosarcoma Soft Tissue Sarcoma
• Osteosarcoma
• Rhabdomyosarcoma

Interventions

DRUG

Simvastatin

The starting dose of simvastatin will be 140 mg/m\^2/dose BID for 21 days for the first group. Dose escalation for subsequent groups will be 180 mg/m\^2/dose BID, 225 mg/m\^2/dose BID, and 290 mg/m\^2/dose BID. If the maximum tolerated dose (MTD) has been exceeded at the first dose level, then the subsequent cohort of subjects will be treated at a dose of 100 mg/m2/dose BID (dose level 0). Simvastatin will be administered orally twice daily, approximately 12 hours apart. Feeding tube (nasogastric tube or gastrostomy tube, NOT a jejunum localized tube) administration is allowed. If a subject vomits a dose of simvastatin, it will not be repeated.

DRUG

Cyclophosphamide

The dose of cyclophosphamide will be fixed at 250 mg/m\^2/dose. Cyclophosphamide will be administered intravenously over 30 minutes once daily for 5 days every 21 days.

DRUG

Topotecan

The dose of topotecan will be fixed at 0.75 mg/m\^2/dose. Topotecan will be administered, after cyclophosphamide, intravenously over 30 minutes once daily for 5 days every 21 days.

DRUG

Myeloid growth factor

Myeloid growth factor (G-CSF or pegylated G-CSF) will be initiated 24-48 hours after the completion of topotecan and cyclophosphamide for all subjects, which would be day 6 or 7. Myeloid growth factor should continue until the absolute neutrophil count is greater than 2,000/mm\^3

Sponsors & Collaborators

• Children's Healthcare of Atlanta

  collaborator OTHER

• Emory University

  lead OTHER

Principal Investigators

• Kelly Goldsmith, MD · Emory University/Children's Healthcare of Atlanta

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

29 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-02-28

Primary Completion

2019-09-22

Completion

2019-09-22

Countries

• United States

Study Locations