Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

Emory University

Status and phase

Completed

Phase 1

Conditions

Osteosarcoma

Neuroblastoma

Rhabdomyosarcoma

Clear Cell Sarcoma

Wilms Tumor

Ewing's Sarcoma

Medulloblastoma

Hepatoblastoma

Retinoblastoma

Germ Cell Tumor

Glioma

Astrocytoma

Rhabdoid Tumor

Renal Cell Carcinoma

Ependymoma

Atypical Teratoid/Rhabdoid Tumor

Treatments

Drug: sirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT01331135

Aflac ST0901 CHOANOME (Other Identifier)

IRB00047016

Details and patient eligibility

About

The best treatment for recurrent cancers or those that do not respond to therapies is not known. Typically, patients with these cancers receive a combination of cancer drugs (chemotherapy), surgery, or radiation therapy. These treatments can prolong their life but may not offer a long-term cure.

This study proposes using a drug called Sirolimus in combination with common chemotherapy drugs to treat patients with recurrent and refractory solid tumors. Sirolimus has been found to inhibit cell growth and to have anti-tumor activity in pediatric solid tumors in previous studies and, therefore, has the potential to increase the effectiveness of the chemotherapy drugs when given together.

This study wil investigate the highest dose of Sirolimus that can be given orally with other oral chemotherapy drugs. Cohorts of 2 subjects will be started at the minimum dose. The dose will be increased in the next 2 subjects as long as there were no major reactions in the previous groups. This study will also seek to learn more about the side effects of sirolimus when used in this combination and what effects the drug has on the white cells and the immune system. Successful use of this drug will impact the cancer population greatly by providing an increased chance of survival to those with resistant or recurrent cancers.

Full description

Sirolimus, is a potent immunosuppressive drug that is approved for use in prevention against allograft rejection following solid organ transplant. It has anti-tumor effects mainly by blocking signals which drive cells from G1 to S phase during cell cycle through inhibition of mTOR, thus inhibiting cell growth. Sirolimus, as well as other mTOR inhibitors, has shown anti-tumor activity in pediatric solid tumor xenografts. Children with relapsed and/or refractory solid tumors are in need of novel therapeutic approaches. One option for these patients is the use of prolonged exposure to low dose antiangiogenic chemotherapy, with agents such as etoposide and cyclophosphamide. In this phase I trial the feasibility and optimal dosing for daily sirolimus, in combination with daily celecoxib, and low dose etoposide alternating with cyclophosphamide, will be determined in children with relapsed and refractory solid tumors. p70S6 kinase inhibition will be used as a surrogate for mTOR inhibition. The potential immunosuppressive effect of sirolimus administered on this schedule will be assessed by serial lymphocyte subsets and assessment of memory T cell number.

Enrollment

18 patients

Sex

All

Ages

Under 30 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

must be <=30 years of age at time of study enrollment
histologic verification of malignancy at original diagnosis or relapsis except in patients with intrinsic brain stem tumors, optic pathway gliomas or patients wtih pineal tumors and evaluations of serum or CSF alpha-fetoprotein or beta-HCG
measurable or evaluable disease
disease state must be one for which there is no known curative therapy
Performance level >=50%
Patients must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy
no evidence of acute graft vs. host disease and >=3 months since transplant
organ function as defined in eligibility section of protocol

Exclusion criteria

patients cannot be pregnant or breast-feeding
patients must agree to use of an effective contraceptive method
no growth factors that support platelet or white cell number or function for at least 7 days prior to enrollment
patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible
patients receiving any other investigational drugs
patients receiving any other anti-cancer drugs
patients who have an uncontrolled infection