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Trial record 1 of 6 for:    UM1CA097452 OR UM1CA228823 | Recruiting Studies
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Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT03320330
Recruitment Status : Recruiting
First Posted : October 25, 2017
Last Update Posted : September 2, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Recurrent Malignant Solid Neoplasm Recurrent Osteosarcoma Refractory Malignant Solid Neoplasm Refractory Osteosarcoma Other: Laboratory Biomarker Analysis Biological: Pepinemab Other: Pharmacological Study Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors
Actual Study Start Date : January 12, 2018
Estimated Primary Completion Date : September 19, 2021
Estimated Study Completion Date : September 19, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (pepinemab)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pepinemab
Given IV
Other Names:
  • moAb VX15/2503
  • VX15/2503

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Maximum tolerated dose and/or recommended phase 2 dose of pepinemab (Part A) [ Time Frame: Up to 28 days ]
    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.

  2. Incidence of toxicities of pepinemab (Parts A-B) [ Time Frame: Up to 3 years ]
    Frequency of patients experiencing at least grade 3 toxicity according to the NCI CTCAE version 5.0.

  3. Half-life [ Time Frame: Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+ ]
    Mean and standard deviation summary statistics for the time required for the serum concentration to fall to 50% of its starting dose.

  4. Time to maximum concentration (T max) [ Time Frame: Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+ ]
    Mean and standard deviation summary statistics for the time at which the maximum (peak) serum concentration occurs.

  5. Maximum concentration (C max) [ Time Frame: Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+ ]
    Mean and standard deviation summary statistics for the maximum (peak) serum concentration.

  6. Area under curve (AUC) [ Time Frame: Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+ ]
    Mean and standard deviation summary statistics for the area under the drug concentration over time curve.

  7. Clearance [ Time Frame: Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+ ]
    Mean and standard deviation summary statistics for the rate of elimination of the drug.

  8. Disease control rate (Part B) [ Time Frame: At 4 months ]
    Frequency of disease control success defined as complete response, partial response or stable disease.

  9. Response (complete response or partial response) (Part B) [ Time Frame: Up to 6th cycle of therapy ]
    Frequency of responses assessed by Response Evaluation Criteria in Solid Tumors 1.1.


Secondary Outcome Measures :
  1. T-lymphocyte saturation [ Time Frame: Up to 3 years ]
    Mean and standard deviation for blood samples that will be evaluated for T-lymphocyte saturation by VX15/2503 utilizing a validated flow-cytometry based assay.

  2. Total soluble SEMA4D [ Time Frame: Up to 3 years ]
    Mean and standard deviation of blood and serum samples evaluated for total soluble SEMA4D through a qualified enzyme-linked immunosorbent assay (ELISA) assay.

  3. Immunogenicity of pepinemab [ Time Frame: Up to 3 years ]
    Mean and standard deviation of immunogenicity assessed in serum through a qualified ELISA.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03320330


  Show 24 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Emily G Greengard COG Phase I Consortium

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT03320330     History of Changes
Other Study ID Numbers: ADVL1614
NCI-2017-01103 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ADVL1614 ( Other Identifier: Pediatric Early Phase Clinical Trial Network )
ADVL1614 ( Other Identifier: CTEP )
UM1CA097452 ( U.S. NIH Grant/Contract )
First Posted: October 25, 2017    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Osteosarcoma
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Sarcoma