Title
Triptorelin and Protection of Ovarian Reserve in Adolescents and Young Adults with Cancer

Description
This phase III trial compares the effect of giving triptorelin vs no triptorelin in preventing ovarian damage in adolescents and young adults (AYAs) with cancer receiving chemotherapy with an alkylating agents. Alkylating agents are part of standard chemotherapy, but may cause damage to the ovaries. If the ovaries are not working well or completely shut down, then it will be difficult or impossible to get pregnant in the future. Triptorelin works by blocking certain hormones and causing the ovaries to slow down or pause normal activity. The triptorelin used in this study stays active in the body for 24 weeks or about 6 months after a dose is given. After triptorelin is cleared from the body, the ovaries resume normal activities. Adding triptorelin before the start of chemotherapy treatment may reduce the chances of damage to the ovaries.

Objective
PRIMARY OBJECTIVES:

I. Determine the feasibility of conducting a cross network, multi-site, randomized clinical trial of triptorelin among newly diagnosed adolescent and young adult (AYA) female cancer patients age < 40 years (exclusive of breast cancer).

II. Measure ovarian reserve via anti-Mullerian hormone (AMH) at 2-years post completion of alkylating agent-containing chemotherapy among randomized patients.

SECONDARY OBJECTIVES:

I. Collect information on the longitudinal trajectory of change in AMH and other ovarian hormone levels from cancer diagnosis to 2 years post cancer treatment completion among randomized patients.

II. Determine the feasibility of measuring estrogen deprivation symptoms (i.e., hot flashes, sexual dysfunction) menstrual pattern, and quality of life among randomized patients.

EXPLORATORY OBJECTIVE:

I. Establish a unique cohort of female AYA patients treated with alkylating agent chemotherapy and randomized to receive or not receive triptorelin, that can be followed long-term to study reproductive health concerns and outcomes as well as genetic risk factors for premature menopause.

Treatment OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive triptorelin intramuscularly (IM) up to 14 days prior to standard chemotherapy. For patients whose chemotherapy exceeds 24 weeks, a second dose of triptorelin may be given 24 weeks after the first dose at the treating physician's discretion. Patients also undergo blood sample collection throughout the study.

ARM B: Patients receive standard chemotherapy. Patients also undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 1 and 2 years.

Key Eligibility Inclusion Criteria:

< 40 years of age at the time of enrollment

Patient must be a post-menarchal female and report that their initial menstrual period occurred > 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)

Newly diagnosed with first cancer, exclusive of breast cancer.



Note: Apart from breast carcinoma, other tumor types originating in the breast are permitted (e.g., sarcoma, lymphoma).



Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.

For patients < 20 years of age at enrollment, the expected alkylator dose must be >/= 4 g/m^2 cumulative cyclophosphamide equivalent dose (CED). For patients >/= 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.

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.

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Leukemia; Liver; Lung; Lymphoma; Melanoma/Skin cancer; Multiple Myeloma; Ovary; Pancreas; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital