Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer

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.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive triptorelin intramuscularly (IM) up to 14 days prior to or within 7 days after the start of 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.

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, or dacarbazine (DTIC).
• Expected cumulative cyclophosphamide equivalent dose (CED):

• For patients < 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m^2 cumulative CED calculated according to the equation and specified drugs listed. Dacarbazine is not an eligible drug in this age group.
• For patients ≥ 20 years of age and < 35 years old at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators listed below that contribute to CED. Dacarbazine is not an eligible drug in this age group.
• For patients ≥ 35 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators listed that contribute to CED and/or dacarbazine, which IS an eligible drug in this age group.

Note that CED includes all administration routes: intravenous (IV), oral (PO), IM.

• The planned total duration of therapy with eligible alkylators is expected to be completed within one year after enrollment. Note: treatment plans with prolonged maintenance periods extending beyond one year are permitted so long as those maintenance treatments are not expected to contain eligible alkylators.
• 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.

Exclusion criteria

• Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
• Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
• Congenital syndromes associated with infertility and decreased ovarian reserve at baseline. For example: Turner's Syndrome, Fragile X premutation carriers, Down syndrome, etc.
• Pre-existing seizure disorder, congenital long QT syndrome, pseudotumor cerebri; history of pulmonary embolism, venous thrombosis, or myocardial infarction. Note: Contact study chairs if questions arise about other pre-existing conditions.
• Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
• Receipt of systemic chemotherapy (except for steroids and intrathecal chemotherapy) more than 7 days prior to study enrollment.
• Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).
• Patients who are pregnant are not eligible. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants for the duration of triptorelin therapy (24 weeks per dose).
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of triptorelin therapy (24 weeks per dose).