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Trial record 1 of 1 for:    denosumab osteosarcoma
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Denosumab in Treating Patients With Recurrent or Refractory Osteosarcoma

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02470091
First received: April 14, 2015
Last updated: July 19, 2017
Last verified: July 2017
  Purpose
This phase II trial studies how well denosumab works in treating patients with osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as denosumab, may block tumor growth in different ways by targeting certain cells.

Condition Intervention Phase
Childhood Osteosarcoma Metastatic Osteosarcoma Recurrent Osteosarcoma Biological: Denosumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Denosumab (NSC# 744010), a RANK Ligand Antibody, for Recurrent or Refractory Osteosarcoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Disease control rate (Cohort I) [ Time Frame: At 4 months ]
    Compared to historical COG experience or denosumab therapy produces an objective response rate greater than 5%.

  • Disease control rate (Cohort II) [ Time Frame: At 12 months ]
    Compared to historical COG experience. Will estimate the relative hazard rate and 95% confidence interval associated with various categories using the proportional hazards regression model with the characteristic of interest as the only variable in the model. The logrank statistic will be used to quantify statistical significance.

  • RECIST response (complete response [CR] or partial response [PR] vs not CR or PR) (Cohort I) [ Time Frame: At 4 months ]
    Compared to historical COG experience or denosumab therapy produces an objective response rate greater than 5%.


Secondary Outcome Measures:
  • Disease control rates for patients with recurrent osteosarcoma limited to bone (Cohort I) [ Time Frame: At 4 months ]
    Confidence intervals will be constructed using the approximate normal distribution of each of the estimates and their asymptotic variances.

  • Disease control rates for patients with recurrent osteosarcoma limited to bone (Cohort II) [ Time Frame: At 12 months ]
    The proportion of patients who experience 12 month disease control will be estimated by the method of Kaplan and Meier. The complementary log-log transformation of the Kaplan-Meier estimate of the 12 month disease control probability will be used to construct confidence intervals of that probability.

  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Minimum of 2 years ]
    Will use a Bayesian rule to monitor for excessive toxicity. Descriptive analyses of this safety information will be performed and will include the incidence of adverse events, severe adverse events, serious adverse events, and fatal adverse events. Type, frequency, and severity of laboratory abnormalities will also be analyzed. Safety analyses will be performed in aggregate, by cohort, and by age group (=< 18 years and in patients > 18 years of age). The safety of denosumab in adults and adolescents will be compared.

  • Modeling of PK parameters of denosumab [ Time Frame: Days 1, 8, 15, and 22 of course 1, day 1 of courses 2-4 and 7, and days 1 and 15 of course 6 ]
    The presentation of PK values will be segregated according to time point at which the denosumab was administered.

  • Modeling of PD parameters of denosumab [ Time Frame: Days 1, 8, 15, and 22 of course 1, day 1 of courses 2-4 and 7, and days 1 and 15 of course 6 ]
    Sample means, medians and variances will be calculated. Clearance and volume of distribution will be determined. PD will be characterized by uNTx/Cr ratio and c-telopeptide levels. Both of these characteristics will be modeled according to a repeated measures linear regression model. Depending on the fit of the quadratic model, additional terms in powers of time since enrollment may be added to explore how the PD parameters vary with time.

  • Response rate (CR or PR) for patients with recurrent osteosarcoma limited to bone (Cohort I) [ Time Frame: Up to 3 years post-treatment ]
    Confidence intervals will be constructed using the approximate normal distribution of each of the estimates and their asymptotic variances.


Estimated Enrollment: 90
Study Start Date: October 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (denosumab)
Patients receive denosumab SC on day 1 (days 1, 8, and 15 of course 1 only). Treatment repeats every 4 weeks (28 days) for up to 24 months or 26 courses, whichever occurs first, in the absence of disease progression or unacceptable toxicity.
Biological: Denosumab
Given SC
Other Names:
  • AMG 162
  • AMG-162
  • Prolia
  • Xgeva
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether denosumab therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to historical Children's Oncology Group (COG) experience or denosumab therapy produces an objective response rate greater than 5% (Cohort 1).

II. To determine whether denosumab therapy increases the disease control rate at 12 months in patients with recurrent resected osteosarcoma as compared to historical COG experience (Cohort 2).

SECONDARY OBJECTIVES:

I. To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of denosumab in subjects with recurrent osteosarcoma.

II. To describe the tolerability of denosumab in subjects with recurrent osteosarcoma.

III. To report the disease control rate and objective response rate for patients with recurrent osteosarcoma limited to bone.

TERTIARY OBJECTIVES:

I. To investigate biological markers potentially associated with response to denosumab in patients with recurrent osteosarcoma.

OUTLINE:

Patients receive denosumab subcutaneously (SC) on day 1 (days 1, 8, and 15 of course 1 only). Treatment repeats every 4 weeks (28 days) for up to 24 months or 26 courses, whichever occurs first, in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

  Eligibility

Ages Eligible for Study:   11 Years to 49 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female patients must have a bone age of equal to or greater than 12 years of age as determined by local read of appropriate radiographic imaging
  • Male patients must have a bone age of equal to or greater than 14 years of age as determined by local read of appropriate radiographic imaging
  • Patients must have relapsed or become refractory to conventional therapy, with a regimen including some combination of high dose methotrexate, doxorubicin, cisplatin, ifosfamide and etoposide; and have had histologic verification of osteosarcoma at original diagnosis or at the time of recurrence
  • Cohort 1 patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    • Note: Patients in Cohort 1 will be stratified as follows:

      • Stratum 1: Patients >= 11 years of age but < 18 years
      • Stratum 2: Patients >= 11 years of age but < 50 years
  • Cohort 2 patients must have had a complete resection of all sites of metastatic disease within 30 days prior to enrollment

    • Patients will only be eligible after they have undergone complete surgical resection of suspected metastatic disease that is histopathologically confirmed to be osteosarcoma prior to enrollment

      • Note: The definition of complete resections is: gross resection of all disease as per the operating surgeon; post-operative imaging is not required for confirmation of complete resection
    • Patients must undergo resection of any lung lesion meeting criteria for likely metastatic disease, defined as:

      • 3 or more lesions > 5 mm in diameter OR a single lesion > 1 cm
    • Patients with lung as the only site of resected metastatic disease must have refused participation in protocol AOST1421
  • Patient must have adequate 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
  • 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: 11 to < 13 years old; 1.2 (male, female) maximum serum creatinine (mg/dL)
    • Age: 13 to < 16 years old; 1.5 (male), 1.4 (female) maximum serum creatinine (mg/dL)
    • Age: >= 16 years old; 1.7 (male), 1.4 (female) maximum serum creatinine (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]) < 2.5 x ULN for age
  • Serum calcium or albumin-adjusted serum calcium >= 2.0 mmol/L (8.0 mg/dL) and =< 2.9 mmol/L (11.5 mg/dL)
  • 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 known sensitivity to any of the products to be administered during the study (eg, mammalian derived products, calcium or vitamin D)
  • Patients who are receiving other cancer directed therapy at the time of enrollment
  • Patients who have previously received denosumab
  • Patients who have previously received mithramycin, strontium-89, samarium-153 or rhenium
  • Patients receiving bisphosphonates
  • Pre-existing conditions

    • Disorders associated with abnormal bone metabolism
    • Hypocalcemia that is not corrected with oral calcium supplementation
    • Vitamin D < 20 ng/mL
    • Paget's disease
    • Prior history or current evidence of osteonecrosis of the jaw
    • Any dental or oral condition likely to result in disruption of mucosal integrity during denosumab therapy including: active dental or jaw condition requiring oral surgery or tooth extraction; non-healed dental or oral surgery
    • Unstable systemic disease, excluding osteosarcoma, such as unstable proximal renal tubule dysfunction (Fanconi Syndrome) or congestive heart failure
  • Pregnancy and breast feeding

    • Female patients who are pregnant; a pregnancy test is required for female patients of childbearing potential
    • Lactating females who plan to breastfeed their infants
    • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 5 months after the end of study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02470091

Locations
United States, Delaware
Alfred I duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Scott M. Bradfield    904-697-3529      
Principal Investigator: Scott M. Bradfield         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., District of Columbia, United States, 20010
Contact: Jeffrey S. Dome    202-884-2549      
Principal Investigator: Jeffrey S. Dome         
United States, Florida
Nemours Children's Hospital Recruiting
Orlando, Florida, United States, 32827
Contact: Scott M. Bradfield    904-697-3529      
Principal Investigator: Scott M. Bradfield         
All Children's Hospital Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Gregory A. Hale    727-767-2423    HamblinF@allkids.org   
Principal Investigator: Gregory A. Hale         
United States, Illinois
Lurie Children's Hospital-Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: David O. Walterhouse    773-880-4562      
Principal Investigator: David O. Walterhouse         
United States, Louisiana
Ochsner Medical Center Jefferson Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Craig Lotterman    888-562-4763      
Principal Investigator: Craig Lotterman         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Katherine A. Janeway    877-442-3324      
Principal Investigator: Katherine A. Janeway         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Katherine A. Janeway    877-442-3324      
Principal Investigator: Katherine A. Janeway         
United States, Michigan
Saint John Hospital and Medical Center Recruiting
Detroit, Michigan, United States, 48236
Contact: Hadi Sawaf    313-343-3166      
Principal Investigator: Hadi Sawaf         
United States, New York
Albany Medical Center Recruiting
Albany, New York, United States, 12208
Contact: Vikramjit S. Kanwar    518-262-3368      
Principal Investigator: Vikramjit S. Kanwar         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Richard B. Womer    215-590-2810      
Principal Investigator: Richard B. Womer         
Children's Oncology Group Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine A. Janeway    617-632-4994    katherine_janeway@dfci.harvard.edu   
Principal Investigator: Katherine A. Janeway         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Michael W. Bishop       info@stjude.org   
Principal Investigator: Michael W. Bishop         
United States, Virginia
Childrens Hospital-King's Daughters Recruiting
Norfolk, Virginia, United States, 23507
Contact: Eric J. Lowe    757-668-7243      
Principal Investigator: Eric J. Lowe         
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Katherine Janeway, MD Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02470091     History of Changes
Other Study ID Numbers: AOST1321
NCI-2015-00543 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AOST1321 ( Other Identifier: Children's Oncology Group )
AOST1321 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
Study First Received: April 14, 2015
Last Updated: July 19, 2017

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2017