Clinical Trials /

VX15/2503 in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

NCT03205644

Description:

This phase I/II trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) and to see how well it works in treating younger patients with solid tumors that have come back after treatment, or do not respond to treatment. Monoclonal antibodies, such as VX15/2503, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Malignant Solid Tumor
  • Osteosarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: VX15/2503 in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors
  • Official Title: A Phase 1/2 Trial of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ADVL1614
  • SECONDARY ID: NCI-2017-01103
  • SECONDARY ID: ADVL1614
  • SECONDARY ID: ADVL1614
  • SECONDARY ID: UM1CA097452
  • NCT ID: NCT03205644

Conditions

  • Recurrent Malignant Solid Neoplasm
  • Recurrent Osteosarcoma
  • Refractory Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
Anti-SEMA4D Monoclonal Antibody VX15/2503moAb VX15/2503, VX15/2503Treatment (VX15/2503)

Purpose

This phase I/II trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) and to see how well it works in treating younger patients with solid tumors that have come back after treatment, or do not respond to treatment. Monoclonal antibodies, such as VX15/2503, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of VX15/2503
      administered as an intravenous infusion every 14 days to children with recurrent or
      refractory solid tumors. (Part A) II. To define and describe the toxicities of VX15/2503
      administered on this schedule. (Parts A-B) III. To characterize the pharmacokinetics of
      VX15/2503 in children with recurrent or refractory cancer. (Parts A-B) IV. To preliminarily
      define the antitumor activity of VX15/2503 for the treatment of relapsed or refractory
      osteosarcoma. (Part B) V. To determine if VX15/2503 either improves the disease control rate
      at 4 months in patients with recurrent measurable osteosarcoma or produces an objective
      response rate in patients with relapsed or refractory osteosarcoma.

      SECONDARY OBJECTIVES:

      I. To assess the pharmacodynamics of VX15/2503 through VX15/2503 saturation of T-lymphocytes.

      II. To assess the immunogenicity of VX15/2503 in pediatric patients with recurrent or
      refractory cancer.

      OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

      Patients receive VX15/2503 intravenously (IV) over 60 minutes on days 1 and 15. Treatment
      repeats every 28 days for 13 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (VX15/2503)ExperimentalPatients receive VX15/2503 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 courses in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Parts A: Patients with recurrent or refractory solid tumors are eligible, excluding
                 central nervous system (CNS) tumors; patients must have had histologic verification of
                 malignancy at original diagnosis or relapse
    
              -  Part B: Patients with recurrent or refractory osteosarcoma are eligible; patients must
                 have had histologic verification of malignancy at original diagnosis or relapse
    
              -  Parts A: Patients must have either measurable or evaluable disease
    
              -  Part B: Patients must have measurable disease
    
              -  Patient?s current disease state must be one for which there is no known curative
                 therapy or therapy proven to prolong survival with an acceptable quality of life
    
              -  Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 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
                 anti-cancer therapy and must meet the following minimum duration from prior
                 anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
                 numerical eligibility criteria are met, e.g. blood count criteria, the patient is
                 considered to have recovered adequately
    
                   -  Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
    
                        -  >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy
                           (42 days if prior nitrosourea)
    
                   -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
                      reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
                      last dose of agent
    
                   -  Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
                      and toxicity related to prior antibody therapy must be recovered to grade =< 1
    
                   -  Corticosteroids: If used to modify immune adverse events related to prior
                      therapy, >= 14 days must have elapsed since last dose of corticosteroid
    
                   -  Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
                      growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
                      agents that have known adverse events occurring beyond 7 days after
                      administration, this period must be extended beyond the time during which adverse
                      events are known to occur; the duration of this interval must be discussed with
                      the study chair and the study-assigned research coordinator
    
                   -  Interleukins, interferons and cytokines (other than hematopoietic growth
                      factors): >= 21 days after the completion of interleukins, interferon or
                      cytokines (other than hematopoietic growth factors)
    
                   -  Stem cell Infusions (with or without total body irradiation [TBI]):
    
                        -  Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
                           cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
                           >= 84 days after infusion and no evidence of graft versus host disease
                           (GVHD)
    
                        -  Autologous stem cell infusion including boost infusion: >= 42 days
    
                   -  Cellular Therapy: >= 42 days after the completion of any type of cellular therapy
                      (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
    
                   -  Radiation Therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
                      after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
                      50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
    
                   -  Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
                      after systemically administered radiopharmaceutical therapy
    
              -  Patients must not have received prior exposure to VX15/2503
    
              -  Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
    
              -  Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
                 platelet transfusions for at least 7 days prior to enrollment)
    
              -  Patients with known bone marrow metastatic disease will be eligible for study provided
                 they meet the blood counts above (may receive transfusions provided they are not known
                 to be refractory to red cell or platelet transfusions); these patients will not be
                 evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be
                 evaluable for hematologic toxicity for the dose-escalation part of the study; if
                 dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must
                 be evaluable for hematologic toxicity
    
              -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73
                 m^2 or
    
              -  A serum creatinine based on age/gender as follows:
    
                   -  Age: 1 to < 2 years; Male: 0.6 mg/dL; Female: 0.6 mg/dL
    
                   -  Age: 2 to < 6 years; Male: 0.8 mg/dL; Female: 0.8 mg/dL
    
                   -  Age: 6 to < 10 years; Male: 1 mg/dL; Female: 1 mg/dL
    
                   -  Age: 10 to < 13 years; Male: 1.2 mg/dL; Female: 1.2 mg/dL
    
                   -  Age: 13 to < 16 years; Male: 1.5 mg/dL; Female: 1.4 mg/dL
    
                   -  Age: >= 16 years; Male: 1.7 mg/dL; Female: 1.4 mg/dL
    
              -  Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
                 age
    
              -  Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
                 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
    
              -  Serum albumin >= 2 g/dL
    
              -  Pulse oximetry > 94% on room air if there is clinical indication for determination
                 (e.g. dyspnea at rest)
    
              -  All patients and/or their parents or legally authorized representatives must sign a
                 written informed consent; assent, when appropriate, will be obtained according to
                 institutional guidelines
    
              -  Tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the
                 study chair must be notified prior to enrollment
    
            Exclusion Criteria:
    
              -  Pregnant or breast-feeding women will not be entered on this study; 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
    
              -  Patients receiving systemic corticosteroids who have not been on a stable or
                 decreasing dose of corticosteroid for at least 7 days prior to enrollment are not
                 eligible; if used to modify immune adverse events related to prior therapy, >= 14 days
                 must have elapsed since last dose of systemic corticosteroid; Note: patients who are
                 using topical or inhaled corticosteroids are eligible
    
              -  Patients who are currently receiving another investigational drug are not eligible
    
              -  Patients who are currently receiving other anti-cancer agents are not eligible (except
                 leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior
                 to start of protocol therapy)
    
              -  Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
                 graft-versus-host disease post bone marrow transplant are not eligible for this trial
    
              -  Patients who have an uncontrolled infection are not eligible
    
              -  Patients who have received a prior solid organ transplantation 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
          
    Maximum Eligible Age:30 Years
    Minimum Eligible Age:12 Months
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease control rate (Part B)
    Time Frame:At 4 months
    Safety Issue:
    Description:Disease control success will be defined as complete response, partial response or stable disease.

    Secondary Outcome Measures

    Measure:Immunogenicity of VX15/2503
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Will be assessed in serum through a qualified enzyme-linked immunosorbent assay (ELISA). Analyses will be descriptive and exploratory and hypotheses generating in nature.
    Measure:Pharmacodynamics of VX15/2503 defined as VX15/2503 saturation of T-lymphocytes
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Will be assessed in blood and will utilize a validated flow-cytometry based assay. Analyses will be descriptive and exploratory and hypotheses generating in nature.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Children's Oncology Group

    Last Updated

    June 29, 2017