Clinical trial NCT06513962: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hematopoietic and Lymphatic System Neoplasm
Malignant Solid Neoplasm
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
First posted: 2024-07-22
Enrollment: 60
Sex: FEMALE
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 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.

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.
* 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.

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.
* Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted 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).

Primary outcomes:
measure: Number of enrollments of newly diagnosed AYA female cancer patients age < 40 years
timeFrame: Up to 2 years post-chemotherapy
measure: Accrual rates of newly diagnosed AYA female cancer patients age < 40 years
timeFrame: Up to 2 years post-chemotherapy
measure: Anti-mullerian hormone (AMH) levels
timeFrame: At 2 years post-chemotherapy
Secondary outcomes:
measure: Longitudinal AMH along with other ovarian hormone levels
timeFrame: Up to 2 years post-chemotherapy
measure: Estrogen deprivation symptoms: Hot flashes
timeFrame: Up to 2 years post-chemotherapy
measure: Estrogen deprivation symptoms: Headaches
timeFrame: Up to 2 years post-chemotherapy
measure: Estrogen deprivation symptoms: Vaginal/vulvar symptoms
timeFrame: Up to 2 years post-chemotherapy
measure: Estrogen deprivation symptoms: Sexual function
timeFrame: Up to 2 years post-chemotherapy
measure: Sexual Health
timeFrame: Up to 2 years post-chemotherapy
measure: Menstrual patterns
timeFrame: Up to 2 years post-chemotherapy
measure: Global health-related quality of life: Anxiety
timeFrame: Up to 2 years post-chemotherapy
measure: Global health-related quality of life: Fatigue
timeFrame: Up to 2 years post-chemotherapy
measure: Global health-related quality of life: Depression
timeFrame: Up to 2 years post-chemotherapy
measure: Global health-related quality of life: Sleep disturbance
timeFrame: Up to 2 years post-chemotherapy
measure: Global health-related quality of life: Participation in social activities
timeFrame: Up to 2 years post-chemotherapy
Other outcomes:
measure: Reproductive concerns
timeFrame: Up to 2 years post-chemotherapy
measure: Reproductive outcomes
timeFrame: Up to 2 years post-chemotherapy
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Fort Smith
country: United States
facility: Mercy Hospital Fort Smith
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: CARTI Cancer Center
state: Arkansas
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Medical Center
state: Florida
city: Alton
country: United States
facility: OSF Saint Anthony's Health Center
state: Illinois
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Centralia
country: United States
facility: Saint Mary's Hospital
state: Illinois
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Mount Vernon
country: United States
facility: SSM Health Good Samaritan
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Yorkville
country: United States
facility: Rush-Copley Healthcare Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Garden City
country: United States
facility: Central Care Cancer Center - Garden City
state: Kansas
city: Great Bend
country: United States
facility: Central Care Cancer Center - Great Bend
state: Kansas
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Grand Rapids Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Ascension Borgess Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Ascension Borgess Hospital
state: Michigan
city: Muskegon
country: United States
facility: Trinity Health Muskegon Hospital
state: Michigan
city: Niles
country: United States
facility: Corewell Health Lakeland Hospitals - Niles Hospital
state: Michigan
city: Norton Shores
country: United States
facility: Cancer and Hematology Centers of Western Michigan - Norton Shores
state: Michigan
city: Reed City
country: United States
facility: Corewell Health Reed City Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Corewell Health Lakeland Hospitals - Saint Joseph Hospital
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: University of Michigan Health - West
state: Michigan
city: Ballwin
country: United States
facility: Saint Louis Cancer and Breast Institute-Ballwin
state: Missouri
city: Bolivar
country: United States
facility: Central Care Cancer Center - Bolivar
state: Missouri
city: Branson
country: United States
facility: Cox Cancer Center Branson
state: Missouri
city: Cape Girardeau
country: United States
facility: Southeast Cancer Center
state: Missouri
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Joplin
country: United States
facility: Mercy Hospital Joplin
state: Missouri
city: Osage Beach
country: United States
facility: Lake Regional Hospital
state: Missouri
city: Rolla
country: United States
facility: Mercy Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Rolla
country: United States
facility: Phelps Health Delbert Day Cancer Institute
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital South
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Washington
country: United States
facility: Mercy Hospital Washington
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Hospital Oklahoma City
state: Oklahoma
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Memphis
country: United States
facility: Saint Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Saint Mary's
state: Wisconsin
city: Oconto Falls
country: United States
facility: Saint Vincent Hospital Cancer Center at Oconto Falls
state: Wisconsin
city: Sheboygan
country: United States
facility: Saint Vincent Hospital Cancer Center at Sheboygan
state: Wisconsin
city: Sheboygan
country: United States
facility: Sheboygan Phyisicans Group
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Children's Oncology Group
name: Eric J Chow
role: PRINCIPAL_INVESTIGATOR
References: