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Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Children's Healthcare of Atlanta
Information provided by (Responsible Party):
Muna Qayed, Emory University
ClinicalTrials.gov Identifier:
NCT01331135
First received: April 6, 2011
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 2 years after treatment starts ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years post treatment ] [ Designated as safety issue: Yes ]
    To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.

  • anti-tumor activity of sirolimus [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
    To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.

  • evaluate risk of infection [ Time Frame: 2 years post treatment ] [ Designated as safety issue: Yes ]
    To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.


Estimated Enrollment: 24
Study Start Date: April 2011
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01331135

Locations
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Children's Healthcare of Atlanta
Investigators
Principal Investigator: Muna Qayed, MD Children's Healthcare of Atlanta
  More Information

Additional Information:
No publications provided

Responsible Party: Muna Qayed, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01331135     History of Changes
Other Study ID Numbers: IRB00047016, Aflac ST0901 CHOANOME
Study First Received: April 6, 2011
Last Updated: November 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
pediatrics
sirolimus
relapse

Additional relevant MeSH terms:
Astrocytoma
Carcinoma, Renal Cell
Ependymoma
Hepatoblastoma
Medulloblastoma
Neoplasms
Neuroblastoma
Osteosarcoma
Retinoblastoma
Rhabdoid Tumor
Rhabdomyosarcoma
Sarcoma
Sarcoma, Clear Cell
Sarcoma, Ewing
Wilms Tumor
Adenocarcinoma
Carcinoma
Eye Diseases
Eye Neoplasms
Genetic Diseases, Inborn
Glioma
Kidney Diseases
Kidney Neoplasms
Myosarcoma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Bone Tissue
Neoplasms, Complex and Mixed
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on November 24, 2014