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Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors (Aflac ST0901)

Primary Purpose

Ewing's Sarcoma, Osteosarcoma, Astrocytoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sirolimus
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing's Sarcoma focused on measuring pediatrics, sirolimus, relapse

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Children's Healthcare of Atlanta

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sirolimus treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)
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
To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.
anti-tumor activity of sirolimus
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
To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
evaluate risk of infection
To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.

Full Information

First Posted
April 6, 2011
Last Updated
May 27, 2020
Sponsor
Emory University
Collaborators
Children's Healthcare of Atlanta
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1. Study Identification

Unique Protocol Identification Number
NCT01331135
Brief Title
Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
Acronym
Aflac ST0901
Official Title
Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
April 2011 (Actual)
Primary Completion Date
August 9, 2017 (Actual)
Study Completion Date
August 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Children's Healthcare of Atlanta

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
pediatrics, sirolimus, relapse

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sirolimus treatment
Arm Type
Experimental
Arm Description
Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2.
Intervention Type
Drug
Intervention Name(s)
sirolimus
Other Intervention Name(s)
rapamune, cypher, renacept
Intervention Description
daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
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.
Time Frame
2 years after treatment starts
Secondary Outcome Measure Information:
Title
define and describe toxicities of sirolimus
Description
To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.
Time Frame
2 years post treatment
Title
anti-tumor activity of sirolimus
Description
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.
Time Frame
2 years post treatment
Title
evaluate correlation of p70S6 kinase activity
Description
To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
Time Frame
2 years post treatment
Title
evaluate risk of infection
Description
To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.
Time Frame
2 years post treatment

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Muna Qayed, MD
Organizational Affiliation
Children's Healthcare of Atlanta
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31876107
Citation
Qayed M, Cash T, Tighiouart M, MacDonald TJ, Goldsmith KC, Tanos R, Kean L, Watkins B, Suessmuth Y, Wetmore C, Katzenstein HM. A phase I study of sirolimus in combination with metronomic therapy (CHOAnome) in children with recurrent or refractory solid and brain tumors. Pediatr Blood Cancer. 2020 Apr;67(4):e28134. doi: 10.1002/pbc.28134. Epub 2019 Dec 25.
Results Reference
result
Links:
URL
http://www.choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Research/Clinical-Trials/Find-a-Clinical-Trial
Description
Clinical trials website for Children's Healthcare of Atlanta

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Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

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