AzTrials
AzTrials

Recurrent Malignant Solid NeoplasmPhase 1/2NCT03320330

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

A Phase 1/2 study testing Laboratory Biomarker Analysis, Pepinemab and Pharmacological Study in people with Recurrent Malignant Solid Neoplasm and Recurrent Osteosarcoma, run by Children's Oncology Group at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 months to 30 years
What is being tested?
Laboratory Biomarker Analysis, Pepinemab and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
24 sitesUnited States
Study dates
31 Jan 2018to 30 Jun 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 months to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 40Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Yale University

    New Haven, Connecticut, 06520

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Laboratory Biomarker Analysis, Pepinemab, Pharmacological Study
Medical subject headings
Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PepinemabBiological

    Also called moAb VX15/2503, VX15/2503

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT03320330
Study groupRoleWhat they receive
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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pepinemab; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicities

    Frequency (%) of patients with dose limiting toxicities by dose level and study part.

    Measured: Up to 28 days

  2. Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE'

    Frequency of patients experiencing at least grade 3 toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by dose level and study part.

    Measured: Up to 28 days

  3. Half-life

    Mean and standard deviation for the time required for the serum concentration to fall to 50% of its starting dose by dose level and study part.

    Measured: 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+

  4. Time to Maximum Concentration (T Max)

    Mean and standard deviation for the time at which the maximum (peak) serum concentration occurs by dose level and study part.

    Measured: 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+

  5. Maximum Concentration (C Max)

    Mean and standard deviation for the maximum (peak) serum concentration by dose level and study part.

    Measured: 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+

  6. Area Under Curve (AUC)

    Mean and standard deviation for the area under the drug concentration over time curve by dose level and study part.

    Measured: 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+

  7. Clearance

    Mean and standard deviation for the rate of elimination of the drug by dose level and study part.

    Measured: 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+

  8. Disease Control Rate (Part A)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD

    Measured: Up to 4 months

  9. Response (Complete Response or Partial Response) (Part B)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD

    Measured: Up to 168 days

Secondary outcomes (3)

  1. T-lymphocyte Saturation

    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 on cycle 1 day 28 (prior to cycle 2 day 1).

    Measured: Up to 28 days

  2. Total Soluble SEMA4D

    Mean and standard deviation of blood and serum samples evaluated for total soluble SEMA4D through a qualified enzyme-linked immunosorbent assay (ELISA) assay.

    Measured: Up to 28 days

  3. Immunogenicity of Pepinemab

    Mean and standard deviation of immunogenicity assessed in serum through a qualified ELISA.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2017
  2. Study start31 Jan 2018
  3. Primary completion31 Dec 2020
  4. Study completion30 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03320330
Sponsor's protocol ID
ADVL1614
Other IDs
NCI-2017-01103, ADVL1614, ADVL1614, UM1CA097452
Status last verified
Jul 2024
First submitted
13 Oct 2017
Last updated
15 Jul 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Greengard E, Williams R, Moriarity B, Liu X, Minard CG, Reid JM, Fisher T, Evans E, Pastore DR, Zauderer M, Voss S, Fox E, Weigel BJ. A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614). Pediatr Blood Cancer. 2024 Jun;71(6):e30938. doi: 10.1002/pbc.30938. Epub 2024 Mar 23.

    PubMed 38520670

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Laboratory Biomarker Analysis, Pepinemab and Pharmacological Study in people with Recurrent Malignant Solid Neoplasm and Recurrent Osteosarcoma, run by Children's Oncology Group at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (time frame: Up to 28 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03320330, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in