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.
Brief Title
Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Hematopoietic and Lymphatic System Neoplasm
Malignant Solid Neoplasm
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).
* \< 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).
Inclusion 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.
* \< 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.
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
39 Years
NCT Id
NCT06513962
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
ALTE2131
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Triptorelin and Protection of Ovarian Reserve in Adolescents and Young Adults With Cancer
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of enrollments of newly diagnosed AYA female cancer patients age < 40 years
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Description
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.
Outcome Measure
Accrual rates of newly diagnosed AYA female cancer patients age < 40 years
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Description
AMH values will be examined to confirm that the combined variability of AMH in both arms is consistent with our a priori assumptions.
Outcome Measure
Anti-mullerian hormone (AMH) levels
Outcome Time Frame
At 2 years post-chemotherapy
Secondary Ids
Secondary Id
NCI-2024-05414
Secondary Id
ALTE2131
Secondary Id
COG-ALTE2131
Secondary Id
ALTE2131
Secondary Id
UG1CA189955
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Longitudinal AMH along with other ovarian hormone levels
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Estrogen deprivation symptoms: Hot flashes
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Estrogen deprivation symptoms: Headaches
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Estrogen deprivation symptoms: Vaginal/vulvar symptoms
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Estrogen deprivation symptoms: Sexual function
Outcome Description
Sexual dysfunction will be assessed using PROMIS SexFS.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Sexual Health
Outcome Description
Menstrual patterns will be assessed using standard items and characterized according to the Staging of Reproductive Aging Workshop criteria.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Menstrual patterns
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Global health-related quality of life: Anxiety
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Global health-related quality of life: Fatigue
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Global health-related quality of life: Depression
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Global health-related quality of life: Sleep disturbance
Outcome Description
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.
Outcome Time Frame
Up to 2 years post-chemotherapy
Outcome Measure
Global health-related quality of life: Participation in social activities
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
39
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alice Lee
Investigator Email
alee5@montefiore.org