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

May 27, 2020 updated by: Muna Qayed, Emory University

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

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 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.
2 years after treatment starts

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
define and describe toxicities of sirolimus
Time Frame: 2 years post treatment
To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.
2 years post treatment
anti-tumor activity of sirolimus
Time Frame: 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.
2 years post treatment
evaluate correlation of p70S6 kinase activity
Time Frame: 2 years post treatment
To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
2 years post treatment
evaluate risk of infection
Time Frame: 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.
2 years post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Muna Qayed, MD, Children's Healthcare of Atlanta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2011

Primary Completion (Actual)

August 9, 2017

Study Completion (Actual)

August 9, 2017

Study Registration Dates

First Submitted

April 6, 2011

First Submitted That Met QC Criteria

April 6, 2011

First Posted (Estimate)

April 7, 2011

Study Record Updates

Last Update Posted (Actual)

May 29, 2020

Last Update Submitted That Met QC Criteria

May 27, 2020

Last Verified

May 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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