Biospecimen Analysis in Determining Effects of Chemotherapy on Fertility in Osteosarcoma Survivors

Osteosarcoma Clinical Trial

Official title:

Effects of Modern Chemotherapy Regimens on Spermatogenesis and Steroidogenesis in Adolescent and Young Adult (AYA) Survivors of Osteosarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03206450
• Other study ID #: ALTE16C1
• Secondary ID: NCI-2017-01152AL
• Status: Active, not recruiting
• Start date: December 6, 2017
• Est. completion date: June 30, 2028

Study information

• Verified date: April 2024
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 224
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Osteosarcoma

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood and provide saliva and semen samples

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Jim Pattison Children's Hospital	Saskatoon	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
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	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	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
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	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	El Paso Children's Hospital	El Paso	Texas
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
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	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
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	M D Anderson Cancer Center	Houston	Texas
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	East Tennessee Childrens Hospital	Knoxville	Tennessee
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	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Kaiser Permanente-Oakland	Oakland	California
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	AdventHealth Orlando	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	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	Renown Regional Medical Center	Reno	Nevada
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Rady Children's Hospital - San Diego	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Role of genetic susceptibility in the development of impairments in spermatogenesis or steroidogenesis with contemporary regimens for the treatment of osteosarcoma	Analysis will be descriptive in nature and will be used to generate hypotheses for future studies.	Up to 4 years
Primary	Infertility	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.	Up to 4 years
Primary	Follicle stimulating hormone levels	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.	Up to 4 years
Primary	Luteinizing hormone levels	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.	Up to 4 years
Primary	Testosterone levels	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.	Up to 4 years
Primary	Serum inhibin B	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.	Up to 4 years
Primary	Sperm concentration	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.	Up to 4 years
Primary	Sperm morphology	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.	Up to 4 years
Primary	Sperm deoxyribonucleic acid methylation	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.	Up to 4 years