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Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

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ClinicalTrials.gov Identifier: NCT02487979
Recruitment Status : Completed
First Posted : July 2, 2015
Results First Posted : October 15, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies how well glembatumumab vedotin works in treating patients with osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as glembatumumab vedotin, may find tumor cells and help kill them.

Condition or disease Intervention/treatment Phase
Recurrent Osteosarcoma Drug: Glembatumumab Vedotin Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate whether CDX-011 (glembatumumab vedotin) therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to an historical Children's Oncology Group (COG) experience or produces an objective response rate in patients without previous eribulin (eribulin mesylate) treatment.

SECONDARY OBJECTIVES:

I. To assess the feasibility and toxicity profile of CDX-011 in patients with recurrent osteosarcoma.

II. To describe the pharmacokinetics of CDX-011 in adolescents and young adults with recurrent osteosarcoma enrolled at COG sites and COG phase I consortium sites only.

III. To determine if there is a relationship between tumor GPNMB expression by immunohistochemistry (IHC) and response to CDX-011 therapy.

IV. To estimate, in the cohort of patients previously treated with eribulin, the proportion who will experience disease progression during the first 4 months of CDX-011 therapy and the proportion of patients who experience a Response Evaluation Criteria in Solid Tumors (RECIST)-defined complete or partial response.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GPNMB-Targeted Antibody-Drug Conjugate, CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE; NSC# 763737), in Recurrent or Refractory Osteosarcoma
Actual Study Start Date : February 16, 2016
Actual Primary Completion Date : June 30, 2017
Actual Study Completion Date : June 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (glembatumumab vedotin)
Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Drug: Glembatumumab Vedotin
Given IV
Other Names:
  • Antibody-Drug Conjugate CR011-vcMMAE
  • CDX-011
  • CR011-vcMMAE
  • CR011-vcMMAE Immunotoxin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Disease Control Success [ Time Frame: First six cycles (21-day cycle) of protocol therapy ]
    The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521


Secondary Outcome Measures :
  1. Toxicity Associated With Chemotherapy [ Time Frame: Duration of protocol therapy - Up to two years ]
    The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.

  2. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life [ Time Frame: Baseline to 24 hours post infusion on course 1 ]
    Total antibody and antibody-drug conjugate half-life are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

  3. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance [ Time Frame: Baseline to 24 hours post infusion on course 1 ]
    Total antibody and antibody-drug conjugate clearance are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

  4. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve [ Time Frame: Baseline to 24 hours post infusion on course 1 ]
    Total antibody and antibody-drug conjugate areas under the curve are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

  5. Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength [ Time Frame: Prior to the time of enrollment ]
    GPNMB expression by IHC of 0+ to 3+ staining strength as assessed on archived tumor specimens. 0 being no GPNMB expression and 3 indicating strong GPNMB expression.

  6. RECIST Response [ Time Frame: First six cycles (21-day cycle) of protocol therapy ]
    The number of patients who experience a complete or partial response according the RECIST criteria for target lesions complete response (CR) disappearance of all lesions; partial response (PR ) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 49 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse
  • Patients must have measurable disease according to RECIST 1.1, and have relapsed or become refractory to conventional therapy
  • Patient must have archival tumor specimen available for submission
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea)
    • Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
    • Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
    • Monoclonal antibodies: must not have received any monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks, prior to study enrollment
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 75,000/uL (transfusion independent)
  • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] 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:

    • Age 1 to < 2 years (male and female: 0.6 mg/dL)
    • Age 2 to < 6 years (male and female: 0.8 mg/dL)
    • Age 6 to < 10 years (male and female: 1 mg/dL)
    • Age 10 to < 13 years (male and female: 1.2 mg/dL)
    • Age 13 to < 16 years (male: 1.5 mg/dL and female: 1.4 mg/dL)
    • Age >= 16 (male: 1.7 mg/dL and female: 1.4 mg/dL)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 110 U/L; for the purposes of this study the ULN for SGPT is defined as 45 U/L
  • Serum albumin > 2 g/dL
  • Shortening fraction of >= 27% by echocardiogram, or
  • Ejection fraction of >= 50% by radionuclide angiogram
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with > grade 2 neuropathy according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies will be excluded except in cases in which neuropathy is secondary to prior surgery
  • Patients who have previously received CDX-011 (CR011-vc monomethyl auristatin E [MMAE]; CDX-011) or other MMAE-containing agents
  • Patients who have received other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study enrollment
  • Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin; compounds of similar composition include auristatin PHE as an anti-fungal agent, auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and symplostatin 1 as an anti-tumor agent
  • Patients with known central nervous system metastasis are not eligible
  • Patients who have had major surgery within 2 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 2 months after the end of study treatment

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): NCT02487979


  Show 155 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lisa Kopp Children's Oncology Group
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02487979     History of Changes
Other Study ID Numbers: NCI-2015-01037
NCI-2015-01037 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AOST1521
s16-01136
AOST1521 ( Other Identifier: Childrens Oncology Group )
AOST1521 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: July 2, 2015    Key Record Dates
Results First Posted: October 15, 2018
Last Update Posted: October 15, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs