Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer
- Conditions
- Malignant Solid NeoplasmHematopoietic and Lymphatic System Neoplasm
- Interventions
- Other: Best PracticeOther: Electronic Health Record ReviewProcedure: Biospecimen CollectionOther: Survey Administration
- Registration Number
- NCT06513962
- Lead Sponsor
- Children's Oncology Group
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 60
- < 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (triptorelin) Electronic Health Record Review Patients receive triptorelin 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 A (triptorelin) Survey Administration Patients receive triptorelin 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 A (triptorelin) Triptorelin Pamoate Patients receive triptorelin 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 (usual care) Best Practice Patients receive standard chemotherapy. Patients also undergo blood sample collection throughout the study. Arm B (usual care) Biospecimen Collection Patients receive standard chemotherapy. Patients also undergo blood sample collection throughout the study. Arm B (usual care) Electronic Health Record Review Patients receive standard chemotherapy. Patients also undergo blood sample collection throughout the study. Arm B (usual care) Survey Administration Patients receive standard chemotherapy. Patients also undergo blood sample collection throughout the study. Arm A (triptorelin) Biospecimen Collection Patients receive triptorelin 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.
- Primary Outcome Measures
Name Time Method Number of enrollments of newly diagnosed AYA female cancer patients age < 40 years Up to 2 years post-chemotherapy Number of enrollments by the end of the DOD funded grant period, and ideally prior to Year 4 to enable greater duration of follow-up time. Will help determine if a larger efficacy study can be successfully completed as a cross network trial in a reasonable funding period.
Accrual rates of newly diagnosed AYA female cancer patients age < 40 years Up to 2 years post-chemotherapy Accrual rates of newly diagnosed AYA female cancer patients age \< 40 years. Over the second half of the funding period, demonstrate a positive trajectory in accrual rates that provides data to inform future funding proposals that would seek to complete the overall larger study within a typical 5-year funding period.
Anti-mullerian hormone (AMH) levels At 2 years post-chemotherapy AMH values will be examined to confirm that the combined variability of AMH in both arms is consistent with our a priori assumptions.
- Secondary Outcome Measures
Name Time Method Longitudinal AMH along with other ovarian hormone levels Up to 2 years post-chemotherapy These measurements will help inform rates of missingness. Will be used to estimate the longitudinal trajectory of change in these hormones by triptorelin randomization status.
Estrogen deprivation symptoms: Hot flashes Up to 2 years post-chemotherapy Estrogen deprivation symptoms include hot flashes. The Patient-Reported Outcomes version of the Common Terminology for Adverse Events (PRO-CTCAE) will be used to collect information on the frequency and interference of hot flashes.
Estrogen deprivation symptoms: Headaches Up to 2 years post-chemotherapy Estrogen deprivation symptoms include headaches. The Patient-Reported Outcomes version of the Common Terminology for Adverse Events (PRO-CTCAE) will be used to collect information on the frequency and interference of headaches.
Estrogen deprivation symptoms: Vaginal/vulvar symptoms Up to 2 years post-chemotherapy Estrogen deprivation symptoms include vaginal/vulvar symptoms. The Patient-Reported Outcomes version of the Common Terminology for Adverse Events (PRO-CTCAE) will be used to collect information on the frequency and interference of vaginal/vulvar symptoms. The PROMIS Sexual Function and Satisfaction version (v) 2.0 Brief Profile - Female (PROMIS SexFS) will be used to evaluate vaginal and vulvar discomfort, pain, and lubrication.
Estrogen deprivation symptoms: Sexual function Up to 2 years post-chemotherapy Estrogen deprivation symptoms include sexual function. The Patient-Reported Outcomes version of the Common Terminology for Adverse Events (PRO-CTCAE) will be used to collect information on the frequency and interference of sexual function. The PROMIS Sexual Function and Satisfaction version (v) 2.0 Brief Profile - Female (PROMIS SexFS) will be used to evaluate sexual activity, desire, and satisfaction among all participants.
Sexual Health Up to 2 years post-chemotherapy Sexual dysfunction will be assessed using PROMIS SexFS.
Menstrual patterns Up to 2 years post-chemotherapy Menstrual patterns will be assessed using standard items and characterized according to the Staging of Reproductive Aging Workshop criteria.
Global health-related quality of life: Anxiety Up to 2 years post-chemotherapy Global health-related quality of life will be assessed using the PROMIS 29 Profile v2.1, which includes assessment of anxiety. For adolescent participants, the PROMIS Pediatric Profile-25 v2.0 will be used to measure health domains.
Global health-related quality of life: Fatigue Up to 2 years post-chemotherapy Global health-related quality of life will be assessed using the PROMIS 29 Profile v2.1, which includes assessment of fatigue. For adolescent participants, the PROMIS Pediatric Profile-25 v2.0 will be used to measure health domains.
Global health-related quality of life: Depression Up to 2 years post-chemotherapy Global health-related quality of life will be assessed using the PROMIS 29 Profile v2.1, which includes assessment of depression. For adolescent participants, the PROMIS Pediatric Profile-25 v2.0 will be used to measure health domains.
Global health-related quality of life: Sleep disturbance Up to 2 years post-chemotherapy Global health-related quality of life will be assessed using the PROMIS 29 Profile v2.1, which includes assessment of sleep disturbance. For adolescent participants, the PROMIS Pediatric Profile-25 v2.0 will be used to measure health domains, with the addition of the PROMIS Pediatric Sleep Disturbance 4a scale.
Global health-related quality of life: Participation in social activities Up to 2 years post-chemotherapy Global health-related quality of life will be assessed using the PROMIS 29 Profile v2.1, which includes assessment of participation in social activities. For adolescent participants, the PROMIS Pediatric Profile-25 v2.0 will be used to measure health domains.
Trial Locations
- Locations (80)
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Lake Regional Hospital
🇺🇸Osage Beach, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Phelps Health Delbert Day Cancer Institute
🇺🇸Rolla, Missouri, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
CARTI Cancer Center
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Saint Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
OSF Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
SSM Health Good Samaritan
🇺🇸Mount Vernon, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Hospital
🇺🇸Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
🇺🇸Nashville, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Sheboygan Phyisicans Group
🇺🇸Sheboygan, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States