Biospecimen Analysis in Determining Effects of Chemotherapy on Fertility in Osteosarcoma Survivors
- Conditions
- Osteosarcoma
- Interventions
- Procedure: Biospecimen CollectionOther: Laboratory Biomarker AnalysisOther: Questionnaire Administration
- Registration Number
- NCT03206450
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This research trial studies saliva, semen, and blood samples to determine effects of chemotherapy on fertility in osteosarcoma survivors. Study biospecimen samples from osteosarcoma survivors in the laboratory may help doctors learn whether chemotherapy causes fertility problems and to learn more about the long term effects.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine whether infertility and/or biomarkers of spermatogenesis and steroidogenesis differ in male osteosarcoma survivors treated with cisplatin with or without ifosfamide compared to male controls without a history of cancer.
II. Evaluate whether cisplatin with or without ifosfamide for the treatment of osteosarcoma alters sperm deoxyribonucleic acid (DNA) methylation.
EXPLORATORY OBJECTIVES:
I. Evaluate the role of genetic susceptibility in the development of impairments in spermatogenesis or steroidogenesis with contemporary regimens for the treatment of osteosarcoma.
OUTLINE:
Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 224
-
Received upfront therapies for osteosarcoma, which included cisplatin, (with or without other agents)
-
Patient must have completed cancer treatment >= 2 years prior to study enrollment
-
Osteosarcoma survivors without a systemically treated relapse or subsequent malignancy
- Note: History of relapse or second malignancy is permitted if treated with local therapy only (e.g. surgery, radiation)
-
Able to speak, read and write in English, French or Spanish
-
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
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Observational (questionnaire, biospecimen collection) Biospecimen Collection Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood. Observational (questionnaire, biospecimen collection) Laboratory Biomarker Analysis Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood. Observational (questionnaire, biospecimen collection) Questionnaire Administration Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood.
- Primary Outcome Measures
Name Time Method Infertility Up to 4 years The American Society of Reproductive Medicine's definition of "infertility" as "... the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse" will be used to categorize patients as to a history of infertility. Based on interview questions regarding each subject's personal and partner's history of medical investigations and treatment for infertility, an attempt will be made to further distinguish each subject's history of infertility as being due to the male (study subject), the female or indeterminate. Will determine whether infertility differ in male osteosarcoma survivors treated with cisplatin with or without ifosfamide compared to male controls without a history of cancer. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Sperm concentration Up to 4 years Sperm concentration (per mL) will be assessed by Computer Assisted Sperm Analysis. Three separate counts will be performed and the results averaged. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Luteinizing hormone levels Up to 4 years Will be measured by immunofluorometric assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Testosterone levels Up to 4 years Will be measured by radioimmunoassay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Follicle stimulating hormone levels Up to 4 years Will be measured by immunofluorometric assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Serum inhibin B Up to 4 years Will be measured by enzyme-linked immunosorbent assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Sperm morphology Up to 4 years Sperm morphology will be assessed. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice.
Sperm deoxyribonucleic acid methylation Up to 4 years Genome-wide differentially methylated regions will be identified using methylated deoxyribonucleic acid immunoprecipitation followed by next generation sequencing analysis methylated deoxyribonucleic acid immunoprecipitation sequencing using pooled deoxyribonucleic acid. Sperm deoxyribonucleic acid differentially methylated regions will be confirmed in the pooled samples by bisulfite treatment of genomic deoxyribonucleic acid to convert cytosine to thymine followed by next generation sequencing for a bisulfite-sequencing analysis. Thus, methylated deoxyribonucleic acid immunoprecipitation- sequencing is used to identify the differentially methylated regions and bisulfite sequencing used to confirm the differentially methylated regions at the CpG level resolution. Pyrosequencing will be used involving next generation sequencing after polymerase chain reaction of individual sperm deoxyribonucleic acid samples to assess individual differentially methylated regions.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (99)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, 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 Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University Pediatric Hospital
🇵🇷San Juan, Puerto Rico
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Yale University
🇺🇸New Haven, Connecticut, United States
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Jim Pattison Children's Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States