Current Research Studies

Cancer – NIH R01 Umbrella Study: Effects of Modern Chemotherapy Regimens on Spermatogenesis and Steroidogenesis in Adolescents and Young Adults (AYA) Survivors of Osteosarcoma

Condition or Therapy:



Cancer and Blood Disorders

What is the goal of this study?

Among the most important challenges faced by male childhood and adolescent and young adult (AYA) cancer survivors is the reproductive toxicity of cancer chemotherapy. Cisplatin and Ifosfamide form the backbone of chemotherapy for some of the most common childhood and young adult cancers, but there is a gap in knowledge regarding the effects of cisplatin, and the effects of ifosfamide without cyclophosphamide, on spermatogenesis and steroidogenesis in male AYA survivors of childhood cancer and non-germ cell cancer populations. DNA methylation changes are a possible mechanism of action of these drugs on testicular function. A better understanding of these effects will allow for identification of high risk patients and better prevention strategies for testicular toxicity to be developed for pediatric and AYA cancer treatment protocols. This study will comprehensively evaluate the effects of cisplatin with or without ifosfamide on spermatogenesis and steroidogenesis among childhood and AYA survivors treated with modern chemotherapies for osteosarcoma. Specifically, our aims are: 1) 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; 2) Evaluate whether cisplatin with or without ifosfamide for the treatment of osteosarcoma is associated with sperm DNA methylation patterns. Completion of the proposed research will be a major step towards informing male childhood and AYA cancer patients receiving similar regimens about the adverse effects of their treatment and towards identifying high risk groups that would benefit from targeted strategies for fertility preservation.

Who can join the study?

Researchers are looking for two groups to participate in this study.

Group 1:

  • Male osteosarcoma survivors, between 18 and 50 years old, who received upfront therapy for their osteosarcoma that included cisplatin (with or without agents) and have completed their cancer treatment at least 2 years prior to enrolling in this study. Participants cannot have had a systemically treated relapse or systemically treated other malignancy (local treatment like surgery or radiation for subsequent malignancy is OK).

Group 2:

  • Healthy men, between 18 and 50 years old, with no history of cancer (other than non-melanoma skin cancer) who can speak, read and write in English. Participants must live within a specified distance from the address of an osteosarcoma survivor.

What will happen if my child takes part in this study?

Osteosarcoma survivors will be recruited through their treatment institutions and controls identified and recruited through address-based sampling. Subjects will complete questionnaires and provide blood, saliva, and semen samples through a mail protocol. Blood samples will be analyzed for testosterone, FSH, LH, Inhibin B; genomic DNA extracted from saliva and stored for future studies of host genetic variation in metabolism of chemotherapeutic drugs storage; and sperm DNA will be assayed using genome-wide methylated DNA immunoprecipitation followed by next generation sequencing. Study participants who complete all study tasks will receive a seminal fluid analysis and a $100 gift card.

Who can I contact for more information?

To learn more, call 877-311-3922 or email the Data Coordinating Center study staff.

Study Location(s):

Seattle Children's Main Hospital Campus
Other: COG participating sites in the U.S. and Canada

Principal Investigator:

Dr. Margarett Shnorhavorian