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

NCT01836549 | Terminated Phase 2 Results DMC

• 3 other identifiers: PBTC-036NCI-2013-00482U01CA081457
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 11

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.

Conditions

Anaplastic Astrocytoma; Anaplastic Ependymoma; Astrocytoma, Grade II; Ependymoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Oligodendroglioma; Brainstem Tumors

Outcome Measures

Primary Outcomes (2)

• Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction

  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.

  Up to 30 days

• Phase II: Stratum-specific Objective Response (CR+PR) Rate

  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.

  6 months

Secondary Outcomes (4)

• Number of Participants With Telomerase Inhibition

  Up to 30 days

• Stratum-specific Progression-free Survival (PFS) (Phase II)

  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

• 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

  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.

• Quantitative MRI Parameters of Tumors Prior to and After Treatment With Imetelstat (Molecular Biology and Phase II Studies)

  Up to 30 days

Study Arms (1)

Treatment (imetelstat sodium)

EXPERIMENTAL

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

Interventions

imetelstat sodium DRUG

Given IV

Also known as: GRN163L, telomerase inhibitor GRN163L

Treatment (imetelstat sodium)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 \[ULN\])

You may not qualify if:

• 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):
• weeks prior to study registration for local palliative XRT (small volume)
• months prior to study registration for craniospinal XRT
• 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
• 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

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Lurie Children's Hospital- Chicago

Chicago, Illinois, 60614, United States

Location

NCI - Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105-2794, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

MeSH Terms

Conditions

Astrocytoma; Ependymoma; Glioblastoma; Gliosarcoma; Oligodendroglioma; Brain Stem Neoplasms

Interventions

imetelstat; GRN163L peptide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Mehmet Kocak
• Organization: University of Tennessee Health Science Center

mkocak1@uthsc.edu

9014482937

Study Officials

• Maryam Fouladi

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 22, 2013
• Study Start: March 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 20, 2018
• Results First Posted: July 20, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)