Ewing's SarcomaPhase 1Aflac ST0901NCT01331135
Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
A Phase 1 study testing sirolimus in people with Ewing's Sarcoma and Osteosarcoma, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Ewing's Sarcoma, Osteosarcoma, Astrocytoma
- What is being tested?
- sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to 9 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: 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.
Read the 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.
- Conditions
- Ewing's Sarcoma, Osteosarcoma, Astrocytoma, Atypical Teratoid/Rhabdoid Tumor, Ependymoma, Germ Cell Tumor
- Being tested
- sirolimus
- Keywords
- pediatrics, sirolimus, relapse
- Medical subject headings
- Sarcoma, Ewing, Osteosarcoma, Astrocytoma, Rhabdoid Tumor, Ependymoma, Neoplasms, Germ Cell and Embryonal, Glioma, Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called rapamune, cypher, renacept
daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| sirolimus treatment | Experimental | Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2. Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years after treatment starts
Secondary outcomes (4)
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.
Measured: 2 years post treatment
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.
Measured: 2 years post treatment
evaluate correlation of p70S6 kinase activity
To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
Measured: 2 years post treatment
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.
Measured: 2 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2011 (estimated)
- Study startApr 2011
- Primary completion9 Aug 2017
- Study completion9 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Responsible party
- Principal investigator, Muna Qayed, Emory University
- Investigators
- Muna Qayed, MD, Principal investigator, Children's Healthcare of Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01331135
- Sponsor's protocol ID
- IRB00047016
- Other IDs
- Aflac ST0901 CHOANOME
- Acronym
- Aflac ST0901
- Status last verified
- May 2020
- First submitted
- 6 Apr 2011
- Last updated
- 29 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31876107
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study
- ClinicalTrials.gov ID
- NCT01331135
- Acronym / sponsor ID
- Aflac ST0901 / IRB00047016
- Conditions
- Ewing's Sarcoma, Osteosarcoma, Astrocytoma, Atypical Teratoid/Rhabdoid Tumor, Ependymoma, Germ Cell Tumor
- Keywords
- pediatrics, sirolimus, relapse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Study start
- Apr 2011 (actual)
- Primary completion
- 9 Aug 2017 (actual)
- Study completion
- 9 Aug 2017 (actual)
- First posted
- 7 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sirolimus treatment | Experimental | Drug: sirolimusDose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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%
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimusAlso: rapamune, cypher, renaceptdaily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2. | Drug | sirolimus treatment |
Primary outcome
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.
4 secondary outcomes
define and describe toxicities of sirolimus
Time frame: 2 years post treatment
anti-tumor activity of sirolimus
Time frame: 2 years post treatment
evaluate correlation of p70S6 kinase activity
Time frame: 2 years post treatment
evaluate risk of infection
Time frame: 2 years post treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2020.
- Results publication: PubMed 31876107Qayed 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.
- Clinical trials website for Children's Healthcare of AtlantaLink provided by the sponsor.
Related trials for Ewing's Sarcoma
Active, not recruitingPhase 3
Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma
Metastatic Ewing Sarcoma, Metastatic Malignant Neoplasm in the Bone
Active, not recruitingPhase 2
CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma
Sarcoma, Ewing, Neoplasm Metastasis
Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Active, not recruitingPhase 2
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
Malignant Solid Neoplasm, Recurrent Adrenal Gland Pheochromocytoma
RecruitingPhase 2
XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma, Bone Sarcoma or Translocation-associated Soft Tissue Sarcoma
Metastatic Leiomyosarcoma, Unresectable Leiomyosarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muna Qayed, MD principal investigator
Children's Healthcare of Atlanta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sirolimus in people with Ewing's Sarcoma and Osteosarcoma, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 2 years after treatment starts). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01331135, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2020.