Clinical trial NCT06246357: Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism
Official title: Phase 2 Study Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hyperaldosteronism
Hypercortisolism
Cushing s Syndrome
Keywords: Adenomas
PET Imaging
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2024-02-07
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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 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.

Eligibility criteria: * 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 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.

Primary outcomes:
measure: Estimate the percent concordance of [68Ga]Ga-PentixaFor imaging with clinical diagnosis in identifying functional adrenal or extra-adrenal adenomas in hyperaldosteronism and hypercortisolism
timeFrame: Screening
Secondary outcomes:
measure: Compare [68Ga]Ga-PentixaFor uptake to C-X-C chemokine receptor type 4 (CXCR4) expression in resected tissue (when obtained on parent protocol)
timeFrame: Within 1 year following [68Ga]Ga-PentixaFor imaging
measure: Evaluate threshold values of [68Ga]Ga-PentixaFor uptake for determining adrenal mass hyperfunction
timeFrame: Within 1 year following [68Ga]Ga-PentixaFor imaging
measure: Estimate the safety of [68Ga]Ga-PentixaFor
timeFrame: Day of [68Ga]Ga-PentixaFor administration until end of study participation
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Maria Liza Lindenberg, M.D.
role: PRINCIPAL_INVESTIGATOR
References: