Ovarian Reserve After Cancer: Longitudinal Effects

Premature Ovarian Failure Clinical Trial

— ORACLE  

Official title:

Ovarian Reserve After Cancer: Longitudinal Effects A Multicenter Prospective Cohort Study by the Oncofertility Consortium

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02467231
• Other study ID #: 809406
• Status: Active, not recruiting
• Start date: February 2009
• Est. completion date: December 2028

Study information

• Verified date: December 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Women of reproductive age who will receive treatment for cancer that includes chemotherapy may participate in a study measuring ovarian function over time. Eligible women are asked to complete a questionnaire, a menstrual diary, a brief physical examination, an ultrasound, and a blood test before, during and after cancer treatment.

Description:

A total of 7 study visits will be completed at 3 month intervals including 1 visit prior to treatment, and at least 2 visits after completion of treatment. Duration of study participation is 18-30 months, depending on length of treatment. Review and Documentation of Cancer Therapy will be abstracted from the clinical oncology chart by the oncology offices caring for the patient. Treatment will be summarized in terms of chemotherapeutic type, duration and cumulative dose; total radiation dose and location; history and type of bone marrow transplantation; and any surgery. Any attempts at fertility preservation or use of gonadotropin releasing hormone agonist treatment during cancer therapy will be captured as well.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 196
• Est. completion date: December 2028
• Est. primary completion date: April 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 11 Years to 35 Years

Eligibility

Inclusion Criteria for exposed population:

• Postmenarchal females to be treated with chemotherapy
• between the ages of 11-35 years,
• with a uterus and at least one ovary

Inclusion Criteria for unexposed population:

• healthy postmenarchal females
• no prior or planned exposure to chemotherapy
• between the ages of 11-35,
• with a uterus and at least one ovary
• regular menstrual cycles (21-35 days)

Exclusion criteria for all subjects:

• positive pregnancy test at enrollment
• lactation within the previous 1 month,
• previous treatment with chemotherapy or radiation therapy with the exception of radioactive iodine for thyroid cancer.
• previous diagnosis of an illness associated with premature ovarian failure (Turner's syndrome, Fragile X permutation carrier)
• endocrine disorder associated with irregular menstrual cycles (Cushing's disease, Thyroid disease, hyper-prolactinemia, congenital adrenal hyperplasia).

Additional exclusions for the unexposed population:

• a history of infertility, defined as at least 12 months of unprotected intercourse without conception
• polycystic ovary syndrome (PCOS)

Related Conditions & MeSH terms

• Effects of Chemotherapy
• Menopause, Premature
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Locations

Country	Name	City	State
United States	University of Pennsylvania, Reproductive Research Unit	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

References & Publications (1)

Dillon KE, Sammel MD, Prewitt M, Ginsberg JP, Walker D, Mersereau JE, Gosiengfiao Y, Gracia CR. Pretreatment antimullerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil Steril. 2013 Feb;99(2):477-83. doi: 10.1016/j.fertnstert.2012.09.039. Epub 2012 Oct 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in menstrual function, during and after chemotherapy	Subjects are asked to document menstrual bleeding in a diary, noting duration of each menstrual period in days, bleeding intensity (spotting, light, moderate, heavy, flooding, none), and intervals between periods.	18-30 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Other	Change from baseline in menopausal symptoms during and after chemotherapy.	The validated "Menopausal Symptom List" (MSL) will be used at each study visit to assess the presence or absence of menopausal symptoms during the past month, the frequency and severity of each symptom. Symptoms captured include: hot flashes, vaginal dryness, concentration/memory problems, irritability, mood swings, feeling sad, feeling anxious, trouble sleeping, aches, joint pain, headaches.	18-30 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Other	Change from baseline in ovarian volume during and after chemotherapy.	Ovaries will be measured in three dimensions. Uterine size and endometrial thickness will also be performed. The transvaginal approach is preferred, but transabdominal ultrasound will be performed in girls who do not feel comfortable with the transvaginal procedure.	18-30 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Primary	Change from baseline in reproductive hormone measures, during and after chemotherapy.	20 mls blood will be obtained at stated timepoints for determining levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Inhibin B, and Anti-mullerian Hormone (AMH). In menstruating girls and young women hormone measures will be obtained during the early follicular phase of the menstrual cycle (days 1-4). In women with irregular cycles the testing will be done spontaneously without regard for the bleeding pattern.	18-30 months: pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Secondary	Change from baseline in antral follicle counts, during and after chemotherapy.	All ovarian follicles and cysts will be measured by transvaginal or transabdominal ultrasound. Follicles will be measured in millimeters and grouped according to size: 2-5 mm, 6-9 mm, and >10 mm in diameter.	18-30 months: pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.