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Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors

Primary Purpose

Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Liver Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Imetelstat Sodium
Laboratory Biomarker Analysis
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatoblastoma

Eligibility Criteria

1 Year - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with any of the following tumors who have relapsed or refractory disease are eligible:

    • Osteosarcoma
    • Ewing?s sarcoma / peripheral primitive neuroectodermal tumor (PNET)
    • Rhabdomyosarcoma
    • Neuroblastoma (measurable or evaluable disease)
    • Hepatoblastoma
  • Patients must have had histologic verification of malignancy at original diagnosis or relapse
  • Patients must have radiographically measurable disease (with the exception of neuroblastoma)

    • Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
    • Note: the following do not qualify as measurable disease:

      • Malignant fluid collections (e.g., ascites, pleural effusions)
      • Bone marrow infiltration
      • Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as defined below for neuroblastoma
      • Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
      • Previously radiated lesions that have not demonstrated clear progression post radiation
      • Leptomeningeal lesions that do not meet the measurements noted above
  • Patients with neuroblastoma who do not have measurable disease but have evaluable disease on 131I-metaiodobenzylguanidine (MIBG) scans are eligible
  • Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Myelosuppressive chemotherapy: patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
  • Hematopoietic growth factors: at least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
  • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
  • Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant
  • For patients with solid tumors without bone marrow involvement:

    • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • For patients with solid tumors without bone marrow involvement:

    • Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • For patients with solid tumors without bone marrow involvement:

    • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions).
  • For patients with solid tumors and known bone marrow metastatic disease:

    • Peripheral absolute neutrophil count (ANC) >= 750/uL
  • For patients with solid tumors and known bone marrow metastatic disease:

    • Platelet count >= 50,000/uL
  • For patients with solid tumors and known bone marrow metastatic disease:

    • Hemoglobin >= 8.0 g/dL

      • Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
  • 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:

    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to < 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin >= 2 g/dL
  • Activated partial thromboplastin time (aPTT) =< 1.2 x upper limit of normal

Exclusion Criteria:

  • Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; study drug may also potentially be secreted in milk and therefore breastfeeding women are excluded
  • Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
  • Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant:

patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial

  • Patients who have an uncontrolled infection are not eligible
  • Patients who have received prior treatment with imetelstat are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  • Patients with prior allogeneic transplants are not eligible

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (imetelstat sodium)

    Arm Description

    Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 36 courses in the absence of disease progression or unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Objective response (complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria or MIBG scoring criteria
    Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. Each disease stratum will be reported separately.
    Incidence of grade 3 or higher adverse events using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    Toxicity tables will be constructed to summarize the observed incidence in each reporting period by type of toxicity and grade. The relative frequency of each type of toxicity will be quantified as the number of toxicity-evaluable cycles in which the adverse event (AE) was noted at grade 3 or higher considered by the treating physician to be possibly, probably or definitely related to one of the agents in the regimen divided by the number of toxicity-evaluable courses administered to patients enrolled on the trial.

    Secondary Outcome Measures

    Progression-free survival
    The probability of remaining progression-free as a function of days since enrollment will be calculated according to the method of Gray accounting for censoring and the competing events.

    Full Information

    First Posted
    December 10, 2013
    Last Updated
    August 3, 2018
    Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02011126
    Brief Title
    Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
    Official Title
    A Phase II Study of Imetelstat (GRN163L, NSC# 754228) in Children With Relapsed or Refractory Solid Tumors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    IND no longer available.
    Study Start Date
    June 30, 2014 (Anticipated)
    Primary Completion Date
    March 25, 2016 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    5. Study Description

    Brief Summary
    This phase II trial studies the side effects and how well imetelstat sodium works in treating younger patients with relapsed or refractory solid tumors. Imetelstat sodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
    Detailed Description
    PRIMARY OBJECTIVES: I. To determine the objective response rate, defined as partial response or better, of imetelstat (imetelstat sodium) in children with relapsed or refractory solid tumors. II. To further define and describe the toxicities associated with imetelstat in children with recurrent/refractory solid tumors. SECONDARY OBJECTIVES: I. To determine the time to progression following treatment with imetelstat in children with relapsed or refractory solid tumors. TERTIARY OBJECTIVES: I. To measure tumor telomere length in archival samples, and to correlate telomere length to the clinical outcome of the study. OUTLINE: Patients receive imetelstat sodium intravenously (IV) over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 36 courses in the absence of disease progression or unacceptable toxicity.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Liver Cancer, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Rhabdomyosarcoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (imetelstat sodium)
    Arm Type
    Experimental
    Arm Description
    Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 36 courses in the absence of disease progression or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    Imetelstat Sodium
    Other Intervention Name(s)
    GRN163L, GRN163L, Sodium Salt
    Intervention Description
    Given IV
    Intervention Type
    Other
    Intervention Name(s)
    Laboratory Biomarker Analysis
    Intervention Description
    Optional correlative studies
    Primary Outcome Measure Information:
    Title
    Objective response (complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria or MIBG scoring criteria
    Description
    Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. Each disease stratum will be reported separately.
    Time Frame
    Up to 126 days (6 courses)
    Title
    Incidence of grade 3 or higher adverse events using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    Description
    Toxicity tables will be constructed to summarize the observed incidence in each reporting period by type of toxicity and grade. The relative frequency of each type of toxicity will be quantified as the number of toxicity-evaluable cycles in which the adverse event (AE) was noted at grade 3 or higher considered by the treating physician to be possibly, probably or definitely related to one of the agents in the regimen divided by the number of toxicity-evaluable courses administered to patients enrolled on the trial.
    Time Frame
    Up to 126 days (6 courses)
    Secondary Outcome Measure Information:
    Title
    Progression-free survival
    Description
    The probability of remaining progression-free as a function of days since enrollment will be calculated according to the method of Gray accounting for censoring and the competing events.
    Time Frame
    Date of enrollment until the end progression-free interval (PFI) date, calculated as the date of disease progression, date of death, date of removal of all tumor by surgery or last patient contact, whichever occurs first, assessed up to 3 years
    Other Pre-specified Outcome Measures:
    Title
    Telomerase length by quantitative polymerase chain reaction
    Description
    The relationship between tumor telomere length and probability of response (as CR or PR) with imetelstat sodium will be assessed using logistic regression.
    Time Frame
    Baseline

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    30 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients with any of the following tumors who have relapsed or refractory disease are eligible: Osteosarcoma Ewing?s sarcoma / peripheral primitive neuroectodermal tumor (PNET) Rhabdomyosarcoma Neuroblastoma (measurable or evaluable disease) Hepatoblastoma Patients must have had histologic verification of malignancy at original diagnosis or relapse Patients must have radiographically measurable disease (with the exception of neuroblastoma) Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm) Note: the following do not qualify as measurable disease: Malignant fluid collections (e.g., ascites, pleural effusions) Bone marrow infiltration Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as defined below for neuroblastoma Elevated tumor markers in plasma or cerebrospinal fluid (CSF) Previously radiated lesions that have not demonstrated clear progression post radiation Leptomeningeal lesions that do not meet the measurements noted above Patients with neuroblastoma who do not have measurable disease but have evaluable disease on 131I-metaiodobenzylguanidine (MIBG) scans are eligible Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study Myelosuppressive chemotherapy: patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea) Hematopoietic growth factors: at least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant For patients with solid tumors without bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/uL For patients with solid tumors without bone marrow involvement: Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) For patients with solid tumors without bone marrow involvement: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions). For patients with solid tumors and known bone marrow metastatic disease: Peripheral absolute neutrophil count (ANC) >= 750/uL For patients with solid tumors and known bone marrow metastatic disease: Platelet count >= 50,000/uL For patients with solid tumors and known bone marrow metastatic disease: Hemoglobin >= 8.0 g/dL Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions 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: 0.6 mg/dL (1 to < 2 years of age) 0.8 mg/dL (2 to < 6 years of age) 1.0 mg/dL (6 to < 10 years of age) 1.2 mg/dL (10 to < 13 years of age) 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age) 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age) Total bilirubin =< 1.5 x upper limit of normal (ULN) for age Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L) Serum albumin >= 2 g/dL Activated partial thromboplastin time (aPTT) =< 1.2 x upper limit of normal Exclusion Criteria: Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; study drug may also potentially be secreted in milk and therefore breastfeeding women are excluded Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim) Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible Patients who are currently receiving another investigational drug are not eligible Patients who are currently receiving other anti-cancer agents are not eligible Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial Patients who have an uncontrolled infection are not eligible Patients who have received prior treatment with imetelstat are not eligible Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Patients with prior allogeneic transplants are not eligible
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Patrick Thompson
    Organizational Affiliation
    Children's Oncology Group
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors

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