Clinical Trials /

Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

NCT03320330

Description:

This phase I/II trial studies the side effects and best dose of pepinemab 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. Immunotherapy with monoclonal antibodies, such as pepinemab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors
  • Official Title: A Phase 1/2 Study 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: NCT03320330

Conditions

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

Interventions

DrugSynonymsArms
PepinemabmoAb VX15/2503, VX15/2503Treatment (pepinemab)

Purpose

This phase I/II trial studies the side effects and best dose of pepinemab 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. Immunotherapy with monoclonal antibodies, such as pepinemab, may help the body's immune system attack the cancer, and 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 pepinemab
      (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. (Part B)

      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.

      EXPLORATORY OBJECTIVES:

      I. To evaluate potential biomarkers of VX15/2503 sensitivity including SEMA4D, PlexinB1, and
      other markers of immune cell infiltration in archival tumor tissues.

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

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

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (pepinemab)ExperimentalPatients receive pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
  • Pepinemab

Eligibility Criteria

        Inclusion Criteria:

          -  Part 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

          -  Part 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)

          -  Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)

          -  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) >= 70
             ml/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

          -  Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 135 U/L;
             for the purpose of this study, the ULN for ALT is 45 U/L

          -  Serum albumin >= 2 g/dL

          -  No clinical indications such as evidence of dyspnea at rest, or exercise intolerance
             due to pulmonary insufficiency

          -  If clinical indications, pulse oximetry > 94% on room air

          -  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 two effective methods of
             birth control, including a medically accepted barrier or contraceptive method (e.g.,
             male or female condom) for the duration of the study; abstinence is an acceptable
             method of birth control

          -  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:Maximum tolerated dose and/or recommended phase 2 dose of pepinemab (Part A)
Time Frame:Up to 28 days
Safety Issue:
Description:Will be defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicities and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Pharmacodynamics of pepinemab defined as pepinemab 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.
Measure:Immunogenicity of pepinemab
Time Frame:Up to 3 years
Safety Issue:
Description:Will be assessed in serum through a qualified ELISA. Analyses will be descriptive and exploratory and hypotheses generating in nature.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Children's Oncology Group

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