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

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ClinicalTrials.gov Identifier: NCT03206450
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : August 26, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date June 27, 2017
First Posted Date July 2, 2017
Last Update Posted Date August 26, 2020
Actual Study Start Date October 10, 2017
Estimated Primary Completion Date October 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 23, 2020)
  • Infertility [ Time Frame: 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.
  • Follicle stimulating hormone levels [ Time Frame: 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.
  • Luteinizing hormone levels [ Time Frame: 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 [ Time Frame: 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.
  • Serum inhibin B [ Time Frame: 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 concentration [ Time Frame: 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.
  • Sperm morphology [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures
 (submitted: June 29, 2017)
  • Follicle stimulating hormone levels [ Time Frame: Up to 4 years ]
    Will be measured by immunofluorometric assay.
  • Infertility [ Time Frame: Up to 12 months ]
    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.
  • Luteinizing hormone levels [ Time Frame: Up to 4 years ]
    Will be measured by immunofluorometric assay.
  • Serum inhibin B [ Time Frame: Up to 4 years ]
    Will be measured by enzyme-linked immunosorbent assay.
  • Sperm concentration [ Time Frame: 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.
  • Sperm deoxyribonucleic acid methylation [ Time Frame: 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- seq
  • Sperm morphology [ Time Frame: Up to 4 years ]
    Sperm morphology will be assessed.
  • Testosterone levels [ Time Frame: Up to 4 years ]
    Will be measured by radioimmunoassay.
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: June 23, 2020)
Role of genetic susceptibility in the development of impairments in spermatogenesis or steroidogenesis with contemporary regimens for the treatment of osteosarcoma [ Time Frame: Up to 4 years ]
Analysis will be descriptive in nature and will be used to generate hypotheses for future studies.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Biospecimen Analysis in Determining Effects of Chemotherapy on Fertility in Osteosarcoma Survivors
Official Title Effects of Modern Chemotherapy Regimens on Spermatogenesis and Steroidogenesis in Adolescent and Young Adult (AYA) Survivors of Osteosarcoma
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
saliva, semen, blood
Sampling Method Non-Probability Sample
Study Population Osteosarcoma survivors who receive upfront therapies for osteosarcoma
Condition Osteosarcoma
Intervention
  • Procedure: Biospecimen Collection
    Undergo collection of blood and provide saliva and semen samples
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Questionnaire Administration
    Ancillary studies
Study Groups/Cohorts Observational (questionnaire, biospecimen collection)
Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood.
Interventions:
  • Procedure: Biospecimen Collection
  • Other: Laboratory Biomarker Analysis
  • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 29, 2017)
331
Original Estimated Enrollment Same as current
Estimated Study Completion Date October 10, 2021
Estimated Primary Completion Date October 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries Canada,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03206450
Other Study ID Numbers ALTE16C1
NCI-2017-01152 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ALTE16C1 ( Other Identifier: Children's Oncology Group )
COG-ALTE16C1 ( Other Identifier: DCP )
ALTE16C1 ( Other Identifier: CTEP )
R01CA175216 ( U.S. NIH Grant/Contract )
UG1CA189955 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Children's Oncology Group
Study Sponsor Children's Oncology Group
Collaborators National Cancer Institute (NCI)
Investigators
Principal Investigator: Margarett Shnorhavorian Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date June 2020