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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hyperaldosteronism; Hypercortisolism; Cushing s Syndrome
• Intervention / Treatment: Drug: [68Ga]Ga-PentixaFor

Detailed 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 any of the following:

  • one or more adrenal masses on CT and/or MRI and biochemical evidence of excess aldosterone or
  • ACTH-independent hypercortisolism with or without adrenal masses on CT and/or MRI 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 up to 1 year to allow the collection of samples for correlative analysis from the parent protocol (adrenal venous sampling, imaging assessments, laboratory evaluations, and/or tissue samples).

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria Liza Lindenberg, M.D.; Phone Number: (240) 760-6109; Email: liza.lindenberg@mail.nih.gov
• Study Contact Backup: Name: Yolanda L McKinney, R.N.; Phone Number: (240) 760-6095; Email: ymckinney@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: National Cancer Institute Referral Office; Phone Number: 888-624-1937

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

• Must have any of the following:

  • one or more adrenal masses on CT and/or MRI and biochemical evidence of excess aldosterone

OR

--ACTH-independent hypercortisolism, with or without adrenal masses on CT and/or MRI

OR

• history of ACTH-dependent hypercortisolism (with or without adrenal enlargement)
• Co-enrollment in 19-DK-0066, 09-C-0242, 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.
• Contraindications to having an MRI and CT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1/[68Ga]Ga-PentixaFor PET/CT or PET/MR; Participants will undergo [68Ga]Ga-PentixaFor PET/CT or PET/MR	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Maria Liza Lindenberg, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2025
• Last Verified: December 5, 2025

More Information

Terms related to this study

• Keywords: PET Imaging; Adenomas
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Adenoma; Cushing Syndrome; Hyperaldosteronism
• Other Study ID Numbers: 10001600; 001600-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No