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

Official title

Triptorelin and Protection of Ovarian Reserve in Adolescents and Young Adults With Cancer

Overview

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.

Detailed description

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.

Interventions

• Other Best Practice
  Receive standard chemotherapy
• Procedure Biospecimen Collection
  Undergo blood sample collection
• Other Electronic Health Record Review
  Ancillary studies
• Other Survey Administration
  Ancillary studies
• Drug Triptorelin Pamoate
  Given IM

Primary outcome measures

• Number of enrollments of newly diagnosed AYA female cancer patients age < 40 years [Time frame: Up to 2 years post-chemotherapy]
• Accrual rates of newly diagnosed AYA female cancer patients age < 40 years [Time frame: Up to 2 years post-chemotherapy]
• Anti-mullerian hormone (AMH) levels [Time frame: At 2 years post-chemotherapy]

Secondary outcome measures (12)

• Longitudinal AMH along with other ovarian hormone levels [Time frame: Up to 2 years post-chemotherapy]
• Estrogen deprivation symptoms: Hot flashes [Time frame: Up to 2 years post-chemotherapy]
• Estrogen deprivation symptoms: Headaches [Time frame: Up to 2 years post-chemotherapy]
• Estrogen deprivation symptoms: Vaginal/vulvar symptoms [Time frame: Up to 2 years post-chemotherapy]
• Estrogen deprivation symptoms: Sexual function [Time frame: Up to 2 years post-chemotherapy]
• Sexual Health [Time frame: Up to 2 years post-chemotherapy]
• Menstrual patterns [Time frame: Up to 2 years post-chemotherapy]
• Global health-related quality of life: Anxiety [Time frame: Up to 2 years post-chemotherapy]
• Global health-related quality of life: Fatigue [Time frame: Up to 2 years post-chemotherapy]
• Global health-related quality of life: Depression [Time frame: Up to 2 years post-chemotherapy]
• Global health-related quality of life: Sleep disturbance [Time frame: Up to 2 years post-chemotherapy]
• Global health-related quality of life: Participation in social activities [Time frame: Up to 2 years post-chemotherapy]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 201 centers

• Children's Hospital of Alabama — Birmingham
• University of Alabama at Birmingham Cancer Center — Birmingham
• USA Health Strada Patient Care Center — Mobile
• Phoenix Childrens Hospital — Phoenix
• Banner University Medical Center - Tucson — Tucson
• Mercy Hospital Fort Smith — Fort Smith
• Arkansas Children's Hospital — Little Rock
• CARTI Cancer Center — Little Rock
• … and 193 more centers

Canada · 4 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06513962 · ALTE2131 · NCI-2024-05414 · ALTE2131 · COG-ALTE2131 · ALTE2131 · UG1CA189955

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗