Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000395437p
Ethics application status
Not yet submitted
Date submitted
10/04/2025
Date registered
2/05/2025
Date last updated
2/05/2025
Date data sharing statement initially provided
2/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
IMmune checkPoint inhibitor related gonAdal toxiCiTy in
premenopausal women and men with melanoma – the
IMPACT study
Scientific title
IMmune checkPoint inhibitor related gonAdal toxiCiTy in
premenopausal women and men with melanoma – the
IMPACT study
Secondary ID [1] 314185 0
Nil known
Universal Trial Number (UTN)
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 337047 0
Hypogonadism 337048 0
Menopause 337049 0
Condition category
Condition code
Cancer 333495 333495 0 0
Malignant melanoma
Metabolic and Endocrine 333496 333496 0 0
Other endocrine disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective study aiming to describe what happens with the gonadal function after receiving immune checkpoint inhibitor (ICI) treatment as part of standard treatment for melanoma in two cohorts of patients: 1) premenopausal woman less than or equal to 45 years and 2) men less than or equal to 60 years.

ICI treatment will be delivered regardless of their involvement in the IMPACT study and will be determined by their treating clinician(s).

Eligible patients will be identified by their medical oncologist at one of the participating sites and informed consent will be obtained.

Contraceptive and menstrual history, sexual function questionnaires and blood for biomarkers of ovarian and testicular function will be collected at 4 timepoints during the
patient’s routine treatment reviews for both cohorts:
1. Before the first dose of ICI
2. 3 months after commencing ICI
3. 6 months after commencing ICI
4. 12 months after commencing ICI

In men (cohort 2), semen will also be collected
1. Before first dose of ICI
2. 6 months after commencing ICI

In a subset of men (cohort 2), testicular volume will also be collected
using an orchidometer
1. Before first dose of ICI
2. 6 months after commencing ICI

For participants in both cohorts who discontinue ICI before 12 months, questionnaires and blood will be collected within 4 weeks after last ICI dose.

As patients on ICI treatment usually have routine clinic visits and blood tests taken during treatment to make sure they are not having any side effects, we aim to collect the additional information, questionnaires and research blood tests at the same time as their routine visits and blood tests.
The anticipated time needed for collection of blood for biomarkers of ovarian and testicular function is anticipated to take 10 minutes per visit, completion of contraceptive and menstrual history and sexual function questionnaires is anticipated to take 15-20 minutes per visit, collection of semen for semen analysis is anticipated to take 30 minutes per visit and measurement of testicular volume using an orchidometer is anticipated to take 10 minutes per visit.
Intervention code [1] 330791 0
Diagnosis / Prognosis
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341073 0
Cohort 1: premenopausal women with curable melanoma, aged less than or equal to 45 years: ovarian reserve (using AMH) within 12 months of ICI treatment
Timepoint [1] 341073 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Primary outcome [2] 341074 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: Testicular function (using testosterone) within 12 months of ICI treatment
Timepoint [2] 341074 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [1] 446072 0
Cohort 1: premenopausal women with curable melanoma, aged less than or equal to 45 years: ovarian function within 12 months of ICI treatment
Timepoint [1] 446072 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [2] 446073 0
Cohort 1: premenopausal women with curable melanoma, aged less than or equal to 45 years: Menstruation within 12 months of ICI treatment
Timepoint [2] 446073 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [3] 446074 0
Cohort 1: premenopausal women with curable melanoma, aged less than or equal to 45 years: Sexual function within 12 months of ICI treatment
Timepoint [3] 446074 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [4] 446075 0
Cohort 1: premenopausal women with curable melanoma, aged less than or equal to 45 years: change in circulating pro-inflammatory cytokines within 12 months of ICI treatment
Timepoint [4] 446075 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [5] 446076 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: testicular function (using FSH, LH, SHBG, inhibin B and related sex steroids by LC-MS) within 12 months of ICI treatment
Timepoint [5] 446076 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [6] 446077 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: change in semen parameters within 6 months of ICI treatment
Timepoint [6] 446077 0
before ICI treatment commencement, and at 6 months after treatment commencement
Secondary outcome [7] 446078 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: Sexual and erectile function within 12 months of ICI treatment
Timepoint [7] 446078 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [8] 446079 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: change in testicular volume within 6 months of ICI treatment
Timepoint [8] 446079 0
before ICI treatment commencement, and at 6 months after treatment commencement
Secondary outcome [9] 446080 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: change in circulating cytokine levels within 12 months of ICI treatment
Timepoint [9] 446080 0
before ICI treatment commencement, and at 3, 6 and 12 months after treatment commencement
Secondary outcome [10] 446500 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: Sexual and erectile function within 12 months of ICI treatment
Timepoint [10] 446500 0
before ICI treatment commencement, and at 3, 6, 12 months after treatment commencement
Secondary outcome [11] 446501 0
Cohort 2: men with curable melanoma, aged less than or equal to 60 years: Sexual and erectile function within 12 months of ICI treatment
Timepoint [11] 446501 0
before ICI treatment commencement, and at 3, 6, 12 months after treatment commencement

Eligibility
Key inclusion criteria
Patients will be eligible for inclusion in this trial if all the following criteria apply:
1. Patient has provided written informed consent using the IMPACT Patient Information and Consent form (PICF)
2. Diagnosis of melanoma (Stage II, III or IV) in the de novo or recurrent setting
3. Has a life expectancy of greater than or equal to 1 year
4. Planned to receive ICI treatment, either in the neoadjuvant, adjuvant or metastatic setting, including as:
• Monotherapy
• Combination therapy

For cohort 1: premenopausal women with melanoma
5. Age greater than or equal to 18 and less than or equal to 45 years at the time of signing consent
6. Patient is premenopausal (defined as baseline FSH within the premenopausal range per local laboratory at registration). Women on hormonal contraception who have an abnormal FSH level, will be included if their AMH level is greater than or equal to 1.0 pmol/L at registration
7. AMH level greater than or equal to 1.0 pmol/L at registration

For Cohort 2: men with melanoma
8. Age greater than or equal to 18 and less than or equal to 60 years at the time of signing consent
9. Fasting morning total testosterone, LH and FSH within the normal range (per local laboratory) at the time registration
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will not be eligible for inclusion in this trial if any of the following criteria apply:
1. Previous removal of both ovaries (females) or previous removal of both testes or previous vasectomy (males)
2. Planned for or previously had pelvic radiotherapy
3. Any medications within the prior 6 months known to disrupt the hypothalamic pituitary gonadal axis, e.g., GnRH agonists or antagonists, selective estrogen receptor modulators (SERMs), aromatase inhibitors, testosterone, anabolic steroids, etc.
4. Previous or concurrent alkylating or platinum-based chemotherapy within the last 2 years
5. Previous use of ICI
6. History of hypogonadism
7. Presence of any psychological, social, geographical, or other condition for which, in the opinion of the site Investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Study design
Purpose
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a prospective study aiming to describe what happens with the gonadal function after receiving ICI treatment for melanoma in two cohorts of patients: premenopausal woman less than or equal to 45 years and men less than or equal to 60 years.

Baseline characteristics and treatment details will be described by Arm using descriptive statistics such as minimum, maximum, median, mean and standard deviation for quantitative variables. Qualitative variables will be described in tabular form as counts and percentages.

No imputation for missing values and no adjustment for multiplicity is intended.
Each cohort will be analysed separately. The primary and secondary endpoints will be reported per participant and in aggregate. For the per participant analysis, each endpoint for each participant will be plotted over time (spaghetti plot) to describe each participant
trajectory. Linear mixed models will be used to summarise the trajectories of each endpoint in each cohort with patients included as random effect. Contrast from the linear mixed models will be used to estimate the mean and 95% confidence intervals at each assessment visit. An exploratory analysis stratifying patients according to ICI duration may be performed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2025
Actual
Date of last participant enrolment
Anticipated
31/12/2026
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 27738 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 27739 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 27740 0
The Poche Centre, Melanoma Institute Australia - North Sydney
Recruitment hospital [4] 27741 0
The Alfred - Melbourne
Recruitment hospital [5] 27742 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [6] 27743 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 27744 0
Cairns Hospital - Cairns
Recruitment postcode(s) [1] 43928 0
3000 - Melbourne
Recruitment postcode(s) [2] 43929 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 43930 0
2060 - North Sydney
Recruitment postcode(s) [4] 43931 0
3084 - Heidelberg
Recruitment postcode(s) [5] 43932 0
6009 - Nedlands
Recruitment postcode(s) [6] 43933 0
4870 - Cairns

Funding & Sponsors
Funding source category [1] 318702 0
Government body
Name [1] 318702 0
Cancer Council Victoria
Country [1] 318702 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
Country
Australia
Secondary sponsor category [1] 321132 0
None
Name [1] 321132 0
Address [1] 321132 0
Country [1] 321132 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 317309 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 317309 0
Ethics committee country [1] 317309 0
Australia
Date submitted for ethics approval [1] 317309 0
12/05/2025
Approval date [1] 317309 0
Ethics approval number [1] 317309 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 140650 0
Dr Wanda Cui
Address 140650 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 140650 0
Australia
Phone 140650 0
+61 3 85595000
Fax 140650 0
Email 140650 0
[email protected]
Contact person for public queries
Name 140651 0
Wanda Cui
Address 140651 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 140651 0
Australia
Phone 140651 0
+61 3 85595000
Fax 140651 0
Email 140651 0
[email protected]
Contact person for scientific queries
Name 140652 0
Wanda Cui
Address 140652 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 140652 0
Australia
Phone 140652 0
+61 3 85595000
Fax 140652 0
Email 140652 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.