Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

Sponsor

Emory University (Other)

Overall Status

Completed

CT.gov ID

NCT01331135

Collaborator

Children's Healthcare of Atlanta (Other)

Enrollment

Location

Arm

76.3

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ewing's Sarcoma Osteosarcoma Astrocytoma Atypical Teratoid/Rhabdoid Tumor Ependymoma Germ Cell Tumor Glioma Medulloblastoma Rhabdoid Tumor Retinoblastoma Clear Cell Sarcoma Renal Cell Carcinoma Wilms Tumor Hepatoblastoma Neuroblastoma Rhabdomyosarcoma	Drug: sirolimus	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study

Actual Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Aug 9, 2017

Actual Study Completion Date :

Aug 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sirolimus treatment Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2.	Drug: sirolimus daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2. Other Names: rapamune cypher renacept

Arm

Intervention/Treatment

Experimental: sirolimus treatment

Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2.

Drug: sirolimus

daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.

Other Names:

rapamune

cypher

renacept

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) [2 years after treatment starts]
estimate the maximum tolerated dose (MTD) and recommended Phase II dose of sirolimus administered orally once daily for 42 days in combination with metronomic chemotherapy in children with recurrent or refractory solid tumors.

Secondary Outcome Measures

define and describe toxicities of sirolimus [2 years post treatment]
To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.
anti-tumor activity of sirolimus [2 years post treatment]
To assess the antitumor activity of sirolimus administered in combination with metronomic chemotherapy to children with recurrent and refractory solid tumors within the confines of a Phase I study.
evaluate correlation of p70S6 kinase activity [2 years post treatment]
To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
evaluate risk of infection [2 years post treatment]
To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 30 Years

Sexes Eligible for Study:

All

Accepts 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