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

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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response (complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria or MIBG scoring criteria

Secondary Outcome

 Progression-free survival

Condition

Hepatoblastoma

Intervention

Imetelstat Sodium

Study Arms / Comparison Groups

 Treatment (imetelstat sodium)
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

June 30, 2014


Primary Completion Date

March 25, 2016

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
      

Gender

All

Ages

1 Year - 30 Years

Accepts Healthy Volunteers

No

Contacts

Patrick Thompson, , 



Administrative Informations


NCT ID

NCT02011126

Organization ID

ADVL1321

Secondary IDs

NCI-2013-01640

Responsible Party

Sponsor

Study Sponsor

Children's Oncology Group

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Patrick Thompson, Principal Investigator, Children's Oncology Group


Verification Date

May 2014