Recurrent Osteosarcoma Clinical Trial
Official title:
Phase 2 Study of Denosumab (NSC# 744010), a RANK Ligand Antibody, for Recurrent or Refractory Osteosarcoma
Verified date | January 2024 |
Source | Children's Oncology Group |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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). Immunotherapy with monoclonal antibodies, such as denosumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Status | Completed |
Enrollment | 56 |
Est. completion date | December 31, 2023 |
Est. primary completion date | December 31, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 11 Years to 49 Years |
Eligibility | 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 - 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 - Note: This applies if AOST1421 is open to enrollment at the enrolling institution on the day the patient consents - 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) 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 mg/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 or planned invasive dental procedures during the anticipated course of study therapy - 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 while on study therapy and through 5 months after completion of study therapy - 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 - 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 |
Country | Name | City | State |
---|---|---|---|
Canada | University of Alberta Hospital | Edmonton | Alberta |
Canada | IWK Health Centre | Halifax | Nova Scotia |
Canada | McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario |
Canada | Children's Hospital | London | Ontario |
Canada | The Montreal Children's Hospital of the MUHC | Montreal | Quebec |
Canada | CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) | Quebec | |
Canada | Hospital for Sick Children | Toronto | Ontario |
Puerto Rico | San Jorge Children's Hospital | San Juan | |
Puerto Rico | University Pediatric Hospital | San Juan | |
United States | Children's Hospital Medical Center of Akron | Akron | Ohio |
United States | Albany Medical Center | Albany | New York |
United States | University of New Mexico Cancer Center | Albuquerque | New Mexico |
United States | Kaiser Permanente-Anaheim | Anaheim | California |
United States | C S Mott Children's Hospital | Ann Arbor | Michigan |
United States | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia |
United States | Children's Hospital Colorado | Aurora | Colorado |
United States | Dell Children's Medical Center of Central Texas | Austin | Texas |
United States | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland |
United States | Sinai Hospital of Baltimore | Baltimore | Maryland |
United States | UHHS-Chagrin Highlands Medical Center | Beachwood | Ohio |
United States | Kaiser Permanente-Bellflower | Bellflower | California |
United States | Walter Reed National Military Medical Center | Bethesda | Maryland |
United States | Children's Hospital of Alabama | Birmingham | Alabama |
United States | Saint Luke's Cancer Institute - Boise | Boise | Idaho |
United States | Brigham and Women's Hospital | Boston | Massachusetts |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University of Vermont and State Agricultural College | Burlington | Vermont |
United States | Centralia Oncology Clinic | Centralia | Illinois |
United States | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina |
United States | University of Virginia Cancer Center | Charlottesville | Virginia |
United States | Lurie Children's Hospital-Chicago | Chicago | Illinois |
United States | University of Chicago Comprehensive Cancer Center | Chicago | Illinois |
United States | University of Illinois | Chicago | Illinois |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Case Western Reserve University | Cleveland | Ohio |
United States | Cleveland Clinic Foundation | Cleveland | Ohio |
United States | Rainbow Babies and Childrens Hospital | Cleveland | Ohio |
United States | Prisma Health Richland Hospital | Columbia | South Carolina |
United States | Nationwide Children's Hospital | Columbus | Ohio |
United States | Driscoll Children's Hospital | Corpus Christi | Texas |
United States | Medical City Dallas Hospital | Dallas | Texas |
United States | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas |
United States | Carle at The Riverfront | Danville | Illinois |
United States | Dayton Children's Hospital | Dayton | Ohio |
United States | Cancer Care Specialists of Illinois - Decatur | Decatur | Illinois |
United States | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado |
United States | Ascension Saint John Hospital | Detroit | Michigan |
United States | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan |
United States | Kaiser Permanente Downey Medical Center | Downey | California |
United States | Carle Physician Group-Effingham | Effingham | Illinois |
United States | Crossroads Cancer Center | Effingham | Illinois |
United States | Sanford Broadway Medical Center | Fargo | North Dakota |
United States | Kaiser Permanente-Fontana | Fontana | California |
United States | Cook Children's Medical Center | Fort Worth | Texas |
United States | University of Florida Health Science Center - Gainesville | Gainesville | Florida |
United States | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | Connecticut Children's Medical Center | Hartford | Connecticut |
United States | Penn State Children's Hospital | Hershey | Pennsylvania |
United States | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii |
United States | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas |
United States | Ascension Saint Vincent Indianapolis Hospital | Indianapolis | Indiana |
United States | Riley Hospital for Children | Indianapolis | Indiana |
United States | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa |
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida |
United States | Bronson Methodist Hospital | Kalamazoo | Michigan |
United States | Children's Mercy Hospitals and Clinics | Kansas City | Missouri |
United States | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada |
United States | Sunrise Hospital and Medical Center | Las Vegas | Nevada |
United States | Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center | Lebanon | New Hampshire |
United States | University of Kentucky/Markey Cancer Center | Lexington | Kentucky |
United States | Arkansas Children's Hospital | Little Rock | Arkansas |
United States | Loma Linda University Medical Center | Loma Linda | California |
United States | Children's Hospital Los Angeles | Los Angeles | California |
United States | Kaiser Permanente Los Angeles Medical Center | Los Angeles | California |
United States | Norton Children's Hospital | Louisville | Kentucky |
United States | Valley Children's Hospital | Madera | California |
United States | Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois |
United States | Saint Jude Children's Research Hospital | Memphis | Tennessee |
United States | Nicklaus Children's Hospital | Miami | Florida |
United States | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida |
United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
United States | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota |
United States | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota |
United States | West Virginia University Healthcare | Morgantown | West Virginia |
United States | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee |
United States | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey |
United States | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey |
United States | Ochsner Medical Center Jefferson | New Orleans | Louisiana |
United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York |
United States | Newark Beth Israel Medical Center | Newark | New Jersey |
United States | Children's Hospital of The King's Daughters | Norfolk | Virginia |
United States | Cancer Care Center of O'Fallon | O'Fallon | Illinois |
United States | UCSF Benioff Children's Hospital Oakland | Oakland | California |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska |
United States | University of Nebraska Medical Center | Omaha | Nebraska |
United States | Children's Hospital of Orange County | Orange | California |
United States | AdventHealth Orlando | Orlando | Florida |
United States | Nemours Children's Hospital | Orlando | Florida |
United States | Saint Jude Midwest Affiliate | Peoria | Illinois |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Children's Oncology Group | Philadelphia | Pennsylvania |
United States | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania |
United States | Phoenix Childrens Hospital | Phoenix | Arizona |
United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
United States | Oregon Health and Science University | Portland | Oregon |
United States | Rhode Island Hospital | Providence | Rhode Island |
United States | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia |
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
United States | University of Rochester | Rochester | New York |
United States | University of California Davis Comprehensive Cancer Center | Sacramento | California |
United States | Mercy Hospital Saint Louis | Saint Louis | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida |
United States | Primary Children's Hospital | Salt Lake City | Utah |
United States | Children's Hospital of San Antonio | San Antonio | Texas |
United States | University of Texas Health Science Center at San Antonio | San Antonio | Texas |
United States | Kaiser Permanente-San Diego Zion | San Diego | California |
United States | Rady Children's Hospital - San Diego | San Diego | California |
United States | UCSF Medical Center-Mission Bay | San Francisco | California |
United States | Maine Children's Cancer Program | Scarborough | Maine |
United States | Seattle Children's Hospital | Seattle | Washington |
United States | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota |
United States | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington |
United States | State University of New York Upstate Medical University | Syracuse | New York |
United States | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida |
United States | Banner University Medical Center - Tucson | Tucson | Arizona |
United States | Carle Cancer Center | Urbana | Illinois |
United States | The Carle Foundation Hospital | Urbana | Illinois |
United States | Children's National Medical Center | Washington | District of Columbia |
United States | Saint Mary's Hospital | West Palm Beach | Florida |
United States | Alfred I duPont Hospital for Children | Wilmington | Delaware |
United States | Wake Forest University Health Sciences | Winston-Salem | North Carolina |
United States | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Children's Oncology Group | National Cancer Institute (NCI) |
United States, Canada, Puerto Rico,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Disease Control Rate (Cohort I) | Disease control interval was calculated as the time from enrolment until detection of new disease or progression of an existing site of disease as determined by the treating physician. Disease control interval of at least 4 months was considered disease control success. | At 4 months | |
Primary | Response Evaluation Criteria in Solid Tumors (RECIST) Response (Complete Response [CR] or Partial Response [PR] vs Not CR or PR) (Cohort I) | Per Response Evaluation Criteria In Solid TumorsCriteria (RECIST v1.0) 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; Overall Response (OR) = CR + PR. | At 4 months | |
Primary | Disease Control Rate (Cohort II) | Disease control interval was calculated as the time from enrolment until detection of new disease as determined by the treating physician. Disease control interval of at least 12 months was considered disease control success. | At 12 months | |
Secondary | Pharmacokinetic (PK) Parameters: Mean of Trough Concentrations of Denosumab | Sample means of trough concentrations of denosumab will be calculated. | 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 | |
Secondary | Pharmacokinetic (PK) Parameters: Median of Trough Concentrations of Denosumab | Sample medians of trough concentrations of denosumab will be calculated. | 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 | |
Secondary | Pharmacodynamic (PD) Parameters of Denosumab: Serum C-telopeptide | Serum c-telopeptide in pg/ml | Days 1, 8, 15, and 22 of course 1 and day 1 of courses 2-4 and 7 | |
Secondary | Pharmacodynamic (PD) Parameters of Denosumab: Urine N-telopeptide to Creatinine Ratio | Urine n-telopeptide to creatinine ratio expressed as nMol BCE/mmol creatinine | Days 1, 8, 15, and 22 of course 1 and day 1 of courses 2-4 and 7 | |
Secondary | Incidence of Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | The number of cycles where a dose-limiting toxicity was identified where dose-limiting toxicity is defined in the protocol using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | Minimum of 2 years | |
Secondary | Response Rate (CR or PR) for Patients With Recurrent Osteosarcoma Limited to Bone (Cohort I) | Confidence intervals will be constructed using the approximate normal distribution of each of the estimates and their asymptotic variances. | Up to 3 years post-treatment | |
Secondary | Disease Control Rates for Patients With Recurrent Osteosarcoma Limited to Bone (Cohort I) | Confidence intervals will be constructed using the approximate normal distribution of each of the estimates and their asymptotic variances. | At 4 months | |
Secondary | Disease Control Rates for Patients With Recurrent Osteosarcoma Limited to Bone (Cohort II) | Disease control interval was calculated at the time from enrolment until detection of new disease as determined by the treating physician. The proportion of patients who experience disease control of at least 12 months will be estimated by the method of Kaplan and Meier. | At 12 months |
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