Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
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|ClinicalTrials.gov Identifier: NCT01836549|
Recruitment Status : Terminated (Due to several intracranial hemorrhages and recommendation by the PBTC DSMB.)
First Posted : April 22, 2013
Results First Posted : July 20, 2018
Last Update Posted : July 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Anaplastic Astrocytoma Anaplastic Ependymoma Astrocytoma, Grade II Ependymoma Giant Cell Glioblastoma Glioblastoma Gliosarcoma Oligodendroglioma Brainstem Tumors||Drug: imetelstat sodium||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Molecular Biology and Phase II Study of Imetelstat (GRN163L) in Children With Recurrent High-Grade Glioma, Ependymoma and Diffuse Intrinsic Pontine Glioma|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
Experimental: Treatment (imetelstat sodium)
Molecular Biology Phase: Patients will receive one infusion of imetelstat prior to surgery. Surgery will take place 12-24 hours after the infusion of imetelstat. Patients will continue to receive therapy on the same schedule as the Phase II patients starting 14-21 days after surgery.
Phase II: Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: imetelstat sodium
- Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction [ Time Frame: Up to 30 days ]This outcome measure is for the Molecular biology study only. The assessment was done to identify cases with at least 50% reduction in telomerase activity.
- Phase II: Stratum-specific Objective Response (CR+PR) Rate [ Time Frame: 6 months ]
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR sustained for at least 6 weeks.
For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. Estimated by cumulative incidence functions.
- Number of Participants With Telomerase Inhibition [ Time Frame: Up to 30 days ]This outcome measure is applicable only for the Molecular biology study arm. Telomerase inhibition was assessed in PBMCs and summarised as 'yes-inhibited' vs. 'no inhibition'
- Stratum-specific Progression-free Survival (PFS) (Phase II) [ Time Frame: Up to 2 years, from the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure, assessed up to 3 years ]Kaplan-Meier estimates of distributions of survival and PFS for all eligible subjects who received at least one dose of imetelstat will be provided separately.
- Number of Patients With Telomerase Expression Data by Detection of hTERT mRNA and TERC RNA Levels by qRT-PCR and Telomerase Activity by TRAP in Archival Tumor Tissue and to Explore Association of Telomerase Positivity With Objective Response and PFS [ Time Frame: Up to 30 days. Due to small number of patients evaluable for this objective, we can only provide number of patients with the targetted markers as no analysis with PFS is possible. ]This secondary objective is for Stratum-B and C only, which enroll HGG and ependymoma patients. We will describe the evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by qRT-PCR and telomerase activity by TRAP in archival tumor tissue; Association of telomerase positivity with objective response and PFS will not be able to be conducted as the study was terminated early and there was no objective response.
- Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies) [ Time Frame: Up to 30 days ]This outcome measure was for both Molecular biology and Phase II studies. We will not be able to present the results of this objective as the study was terminated early.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01836549
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Lurie Children's Hospital- Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Maryland|
|NCI - Pediatric Oncology Branch|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|Saint Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105-2794|
|United States, Texas|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital|
|Houston, Texas, United States, 77030-2399|
|Principal Investigator:||Maryam Fouladi||Pediatric Brain Tumor Consortium|