ClinicalTrials.gov
ClinicalTrials.gov Menu

Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium

Brief Summary:
This molecular biology and phase II trial studies how well imetelstat sodium works in treating younger patients with recurrent or refractory brain tumors. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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
Given IV
Other Names:
  • GRN163L
  • telomerase inhibitor GRN163L




Primary Outcome Measures :
  1. 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.

  2. 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.



Secondary Outcome Measures :
  1. 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'

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • MOLECULAR BIOLOGY STUDY

    • Tumor: Histologically confirmed Dx of ependymoma or HGG (such as anaplastic astrocytoma, glioblastoma, gliosarcoma, or anaplastic oligodendroglioma) that is recurrent or refractory to conventional therapy.
    • Subjects must have clinical indications for surgical resection and be amenable to receiving imetelstat prior to tumor resection. Subjects who require emergent surgery are not eligible for the Molecular Biology study.
    • Subjects must provide, fresh flash frozen tumor samples (target 50 mg tissue; as low as 20 mg is adequate) from the time of diagnosis or previous recurrence for the assessment of tumor telomerase activity by the TRAP assay.
  • PHASE II STUDY

    • Tumor: Subjects must have recurrent or refractory disease with a histological Dx from either the initial presentation or at the time of recurrence. The requirement for histologic verification is waived for subjects with DIPG (stratum D). The following diagnoses are eligible and will be treated in separate strata (B-D): (B) recurrent or refractory high-grade glioma, (such as anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma); (C) recurrent or refractory ependymoma; (D) recurrent or refractory DIPG (diagnosis by imaging characteristics acceptable; no histologic confirmation required)
    • Slides from either initial Dx or relapse must be available for central pathology review for Strata B-C. Tissue slides must be sent per Section 10.1. If tissue slides are unavailable, the study chair must be notified prior to study enrollment.
    • All subjects must have bi-dimensionally measurable disease in the brain and/or spine, defined as at least one lesion that can be accurately measured in at least two planes in order to be eligible for this study. Subjects who are enrolled on the Molecular Biology trial and who have measurable disease after the surgical resection and meet all other eligibility criteria for the Phase II study will be counted towards the accrual of the Phase II study.
  • FOR BOTH MOLECULAR BIOLOGY AND PHASE II STUDIES

    • Subjects with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; a baseline detailed neurological exam should clearly document the neurological status of the subject at the time of registration on the study
    • Karnofsky >= 50% for > 16 years of age; Lansky >= 50% for children < 16 years of age documented within 14 days of study registration and within 7 days of the start of study drug administration
    • Hemoglobin >= 8 g/dL (may receive blood transfusions)
    • Absolute neutrophil count > 1,000/ul
    • Platelet count >= 100,000/ul (transfusion independent defined as no platelet transfusions with a 4 week period prior to enrollment)
    • Serum bilirubin < 2.0 mg/dL (patients with Gilbert syndrome, serum bilirubin < 3.0 x upper limit of normal [ULN])
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x institutional ULN
    • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
    • Alkaline phosphatase < 2.5 x institutional ULN
    • Albumin >= 2 g/dL
    • Adequate coagulation defined as activated partial thromboplastin time (aPTT) < 1.2 x ULN
    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
  • Age 1 to < 2 years: maximum serum creatinine (mg/mL) 0.6 for males and 0.6 for females
  • Age 2 to < 6 years: maximum serum creatinine (mg/mL) 0.8 for males and 0.8 for females
  • Age 6 to < 10 years: maximum serum creatinine (mg/mL) 1 for males and 1 for females
  • Age 10 to < 13 years: maximum serum creatinine (mg/mL) 1.2 for males and 1.2 for females
  • Age 13 to < 16 years: maximum serum creatinine (mg/mL) 1.5 for males and 1.4 for females
  • Age >= 16 years: maximum serum creatinine (mg/mL) 1.7 for males and 1.4 for females
  • The threshold creatinine values were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Centers for Disease and Control (CDC)

    • Subjects on systemic anticoagulants are excluded from this study as the drug can cause minor, transient changes in aPTT
    • Female subjects of childbearing potential must not be pregnant or breast-feeding; female subjects of childbearing potential must have a negative serum or urine pregnancy test; (pregnancy test must be repeated within 48 hours prior to the start of therapy)
    • Subjects of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
    • Subjects must have recovered from the acute toxicities of all prior therapy before entering this study; for those acute baseline adverse events attributable to prior therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0, unless otherwise specified in the Inclusion and Exclusion Criteria
    • Subjects must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration or at least six (6) weeks if nitrosourea
    • Subjects must have received their last dose of investigational or biologic agent >= 7 days prior to study registration; in the event that a subject has received an investigational or biologic agent and has experienced >= grade 2 myelosuppression, then at least three (3) weeks must have elapsed prior to registration; if the investigational or biologic agent has a prolonged half-life (>= 7 days) then at least three (3) weeks must have elapsed prior to registration
    • Subjects must have completed at least 3 half-life periods from the last dose of monoclonal antibody prior to registration; Note: A list of half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) website under Generic Forms and Templates
    • Subjects must have received their last dose of radiation (XRT):
  • 2 weeks prior to study registration for local palliative XRT (small volume)
  • 3 months prior to study registration for craniospinal XRT
  • 6 weeks (wks) prior to study registration for other substantial bone marrow irradiation

    • Subject must be >= 3 months since autologous bone marrow/stem cell transplantation prior to registration
    • Subjects who are receiving a corticosteroid, such as dexamethasone, must be on a stable or decreasing dosage for at least 1 week prior to registration
    • At least 7 days since the completion of therapy with a hematopoietic growth agent (filgrastim, sargramostim, and erythropoietin) and 14 days for long-acting formulations
    • Ability to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

  • Subjects must not be receiving any other investigational agents
  • Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to imetelstat
  • Known coagulopathy or bleeding diathesis
  • Subjects with imaging evidence of CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment are not eligible; Note: The presence of small punctate areas consistent with hemorrhage will not exclude subjects from participation
  • Use of systemic anticoagulant medications
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cirrhosis or psychiatric illness/social situations that would limit compliance with study requirements

Information from the National Library of Medicine

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


Locations
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
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Investigators
Principal Investigator: Maryam Fouladi Pediatric Brain Tumor Consortium

Responsible Party: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT01836549     History of Changes
Other Study ID Numbers: PBTC-036
NCI-2013-00482 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
U01CA081457 ( U.S. NIH Grant/Contract )
First Posted: April 22, 2013    Key Record Dates
Results First Posted: July 20, 2018
Last Update Posted: July 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Other PBTC investigators can develop a concept proposal and submit it to the PBTC Scientific Committee for a decision to share data and to what extent to share it.

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Ependymoma
Gliosarcoma
Oligodendroglioma
Brain Stem Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Infratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases