Recurrent Osteosarcoma
Conditions
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.
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.
Interventions
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 49 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Success | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life | 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 |
| Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance | 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 |
| Toxicity Associated With Chemotherapy | Duration of protocol therapy - Up to two years | The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher. |
| Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength | 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. |
| RECIST Response | 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. |
| Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve | 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 |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Glembatumumab Vedotin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive Disease | 17 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Treatment (Glembatumumab Vedotin) |
|---|---|
| Age, Continuous | 20.09 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 22 |
| other Total, other adverse events | 7 / 22 |
| serious Total, serious adverse events | 8 / 22 |
Outcome results
Primary
Disease Control Success
The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521
Time frame: First six cycles (21-day cycle) of protocol therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Glembatumumab Vedotin) | Disease Control Success | 3 Participants |
Secondary
Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength
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.
Time frame: Prior to the time of enrollment
Population: Analysis was successfully completed for 19 patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Glembatumumab Vedotin) | Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength | 0+ staining strength | 1 Participants |
| Treatment (Glembatumumab Vedotin) | Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength | 1+ staining strength | 3 Participants |
| Treatment (Glembatumumab Vedotin) | Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength | 2+ staining strength | 2 Participants |
| Treatment (Glembatumumab Vedotin) | Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength | 3+ staining strength | 13 Participants |
Secondary
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve
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
Time frame: Baseline to 24 hours post infusion on course 1
Population: Samples were provided for four patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve | Total antibody area under the curve | 2320.0 hour-microgram per millilitre | Standard Deviation 342 |
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve | Antibody-Drug Conjugate area under the curve | 2259.5 hour-microgram per millilitre | Standard Deviation 749.6 |
Secondary
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance
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
Time frame: Baseline to 24 hours post infusion on course 1
Population: Samples were provided for four patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance | Total antibody clearance | 0.8 millilitres per hour per kilogram | Standard Deviation 0.1 |
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance | Antibody-Drug Conjugate clearance | 0.9 millilitres per hour per kilogram | Standard Deviation 0.3 |
Secondary
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life
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
Time frame: Baseline to 24 hours post infusion on course 1
Population: Samples were provided for four patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life | Total antibody half-life | 35.2 hours | Standard Deviation 6.4 |
| Treatment (Glembatumumab Vedotin) | Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life | Antibody-Drug Conjugate half-life | 29.1 hours | Standard Deviation 8.4 |
Secondary
RECIST Response
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.
Time frame: First six cycles (21-day cycle) of protocol therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Glembatumumab Vedotin) | RECIST Response | 1 Participants |
Secondary
Toxicity Associated With Chemotherapy
The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.
Time frame: Duration of protocol therapy - Up to two years
Population: 22 patients were treated on protocol therapy. Sixty-one (61) cycles were reported for the analysis of toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Abdominal Pain | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of acneiform rash | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Anaphylaxis | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Anemia | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Anorexia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Back Pain | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Constipation | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Febrile Neutropenia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Headache | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Hypertension | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Hypocalcemia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Hypokalemia | 4 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Hypophosphatemia | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Hypotension | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Lymphopenia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Mucocitis | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Myalgia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Nausea | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Neutropenia | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Pain | 2 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Pneumothorax | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Thrombocytopenia | 1 cycles |
| Treatment (Glembatumumab Vedotin) | Toxicity Associated With Chemotherapy | Incidence of Leukopenia | 1 cycles |