NCT01331135

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Apr 2011

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2011

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

April 6, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 7, 2011

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 9, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 9, 2017

Completed
Last Updated

May 29, 2020

Status Verified

May 1, 2020

Enrollment Period

6.4 years

First QC Date

April 6, 2011

Last Update Submit

May 27, 2020

Conditions

Keywords

pediatricssirolimusrelapse

Outcome Measures

Primary Outcomes (1)

  • 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.

    2 years after treatment starts

Secondary Outcomes (4)

  • define and describe toxicities of sirolimus

    2 years post treatment

  • anti-tumor activity of sirolimus

    2 years post treatment

  • evaluate correlation of p70S6 kinase activity

    2 years post treatment

  • evaluate risk of infection

    2 years post treatment

Study Arms (1)

sirolimus treatment

EXPERIMENTAL

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

Drug: sirolimus

Interventions

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

Also known as: rapamune, cypher, renacept
sirolimus treatment

Eligibility Criteria

AgeUp to 30 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Sarcoma, EwingOsteosarcomaAstrocytomaRhabdoid TumorEpendymomaNeoplasms, Germ Cell and EmbryonalGliomaMedulloblastomaRetinoblastomaSarcoma, Clear CellCarcinoma, Renal CellWilms TumorHepatoblastomaNeuroblastomaRhabdomyosarcomaRecurrence

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeoplasms, Complex and MixedNeuroectodermal Tumors, PrimitiveRetinal NeoplasmsEye NeoplasmsNeoplasms by SiteEye Diseases, HereditaryEye DiseasesRetinal DiseasesAdenocarcinomaCarcinomaKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesNeoplastic Syndromes, HereditaryGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeuroectodermal Tumors, Primitive, PeripheralMyosarcomaNeoplasms, Muscle TissueDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Study Officials

  • Muna Qayed, MD

    Children's Healthcare of Atlanta

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 6, 2011

First Posted

April 7, 2011

Study Start

April 1, 2011

Primary Completion

August 9, 2017

Study Completion

August 9, 2017

Last Updated

May 29, 2020

Record last verified: 2020-05

Locations