Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism

Hyperaldosteronism Clinical Trial

Official title:

Phase 2 Study Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06246357
• Other study ID #: 10001600
• Secondary ID: 001600-C
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 23, 2024
• Est. completion date: April 1, 2028

Study information

• Verified date: February 7, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Yolanda McKinney, R.N.
• Phone: (240) 760-6095
• Email: ymckinney[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: The adrenal glands are 2 small organs that sit on top of each kidney. They release hormones; these are chemicals that control how the body works. Tumors on or outside the adrenal glands are called functional if they release hormones; they are called nonfunctional if they do not. Doctors who treat adrenal tumors need to know which type a person has. Researchers want to find better ways to learn whether an adrenal tumor is functional. Objective: To see if a new radioactive tracer ([68Ga]Ga-PentixaFor) can make it easier to identify functional adrenal tumors with positron emission tomography (PET) scans. Eligibility: People aged 18 years and older with 1 or more adrenal tumors. They must have increased levels of the hormones aldosterone or cortisol. They must also be enrolled in at least 1 other related NIH study (protocols 19-DK-0066, 18-CH-0031, or 09-C-0242). Design: Participants will be screened. They may have imaging scans. Their ability to perform normal activities will be reviewed. Participants will have one PET scan with the study tracer. The tracer will be given through a tube attached to a needle inserted into a vein. Participants will receive the tracer 1 hour before the scan. They will lie still on a bed while a machine captures images of the inside of their body. The scan will take 45 to 90 minutes. Participants heart rate, blood pressure, and rate of breathing will be checked before, during, and after the scan. Participants will have a follow-up visit 3 days after their scan. This visit can be by phone, email, or in person.

Description:

Background: - [68Ga]Ga-PentixaFor is a PET agent targeting the C-X-C chemokine receptor type 4 (CXCR4) with promising applications in oncology, cardiology, and infectious disease. - CXCR4 has also been noted to show high expression in many aldosterone-producing adenomas (APA) and some cortisol-producing adenomas (CPA) but not usually in nonfunctioning adenomas. - [68Ga]Ga-PentixaFor may be useful in the evaluation of adrenal adenomas in the setting of Conn s or Cushing s syndrome. Localizing functional adenomas is important for managing treatment options but current imaging modalities are either too invasive or insufficiently able to differentiate adrenal conditions. Objective: -To estimate the percent concordance of [68Ga]Ga-PentixaFor imaging with clinical diagnosis in identifying functional adrenal or extra-adrenal adenomas in hyperaldosteronism and hypercortisolism Eligibility: - Must have either of the following: - one or more adrenal masses on CT and/or MRI with biochemical evidence of excess aldosterone or ACTH-independent hypercortisolism, OR - history of ACTH-dependent hypercortisolism (with or without adrenal enlargement). - Age >= 18 years - ECOG performance status <= 2 Design: - This is a Phase II, single site study where participants from three cohorts are enrolled into one arm according to their probable disease: primary aldosteronism (Cohort 1), ACTHindependent Cushing s syndrome (Cohort 2), or ACTH-dependent Cushing s syndrome (Cohort 3). - All participants will undergo a [68Ga]Ga-PentixaFor PET/CT or [68Ga]Ga-PentixaFor PET/MR. - A safety visit will be performed 3 days following the [68Ga]Ga-PentixaFor imaging. - Participants will remain on-study for 1 year until samples are obtained for correlative analysis from the parent protocol (adrenal venous sampling, imaging assessments, laboratory evaluations, and/or tissue samples). - To account for inevaluable participants, the accrual ceiling will be set to 77 maximum participants with the number of evaluable participants enrolled as follows: 20 for Cohort 1, 20 for Cohort 2, and 30 for Cohort 3.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 77
• Est. completion date: April 1, 2028
• Est. primary completion date: December 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

• INCLUSION CRITERIA:
• Must have either of the following:
• one or more adrenal masses on CT and/or MRI with biochemical evidence of excess aldosterone or ACTH-independent hypercortisolism, OR
• history of ACTH-dependent hypercortisolism (with or without adrenal enlargement)
• Co-enrollment in Dr. Nieman (19-DK-0066), Dr. Nilubol (09-C-0242), Dr. Kamilaris (18-CH-0031) or a similar NIH trial.
• Age >=18 years.
• ECOG performance status <= 2.
• Women of child-bearing potential (WOCBP) and men must agree to use an effective contraception (barrier, hormonal, intrauterine device [IUD], surgical sterilization, abstinence) for two weeks prior to [68Ga]Ga-PentixaFor scan and for one week after the [68Ga]Ga-PentixaFor scan.
• Breastfeeding should be discontinued for one week after the [68Ga]Ga-PentixaFor scan.
• Men must agree not to donate sperm for one week after the [68Ga]Ga-PentixaFor scan.
• Participants must be able to understand and willing to sign a written informed consent document.

EXCLUSION CRITERIA:

• Positive beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening.
• Uncontrolled intercurrent illness or social situations based on the review of medical history that would limit compliance with study requirements.

Related Conditions & MeSH terms

• Adrenocortical Hyperfunction
• Cushing Syndrome
• Hyperaldosteronism
• Hypercortisolism

Intervention

Drug:
• [68Ga]Ga-PentixaFor
[68Ga]Ga-PentixaFor will be injected intravenously approximately 60 minutes prior to scanning at a dose of 150 +/- 50 MBq (4 mCi +/- 1.4).

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate the percent concordance of [68Ga]Ga-PentixaFor imaging with clinical diagnosis in identifying functional adrenal or extra-adrenal adenomas in hyperaldosteronism and hypercortisolism	The percent concordance between [68Ga]Ga-PentixaFor and clinical diagnosis will be estimated within each Cohort, along with 90% Clopper-Pearson confidence intervals.	Screening
Secondary	Compare [68Ga]Ga-PentixaFor uptake to C-X-C chemokine receptor type 4 (CXCR4) expression in resected tissue (when obtained on parent protocol)	The Spearman rank correlation coefficient between [68Ga]Ga-PentixaFor PET parameters (SUVmax, SUVmean, TLU, TV) and CXCR4 expression as measured via immunohistochemistry will be estimated within each Cohort.	Within 1 year following [68Ga]Ga-PentixaFor imaging
Secondary	Evaluate threshold values of [68Ga]Ga-PentixaFor uptake for determining adrenal mass hyperfunction	Receiver operating characteristic (ROC) curves of [68Ga]Ga-PentixaFor SUVmax in detecting adrenal mass hyperfunction will be constructed. The cutoff associated with the highest Youden index (sensitivity plus specificity) will be selected as the optimal threshold.	Within 1 year following [68Ga]Ga-PentixaFor imaging
Secondary	Estimate the safety of [68Ga]Ga-PentixaFor	Safety will be evaluated by determining the frequency of adverse events among participants and reporting the results, by maximum grade of event and type of toxicity noted.	Day of [68Ga]Ga-PentixaFor administration until end of study participation

External Links

•   NIH Clinical Center Detailed Web Page