Radioactive Tracer for Cushing's Syndrome

Overseen By Yolanda McKinney, R.N.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Uncontrolled illness, MRI contraindications, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment [68Ga]Ga-PentixaFor for Cushing's Syndrome?

The research shows that [68Ga]Ga-PentixaFor PET/CT is effective in identifying and differentiating adrenal masses, such as aldosterone-producing adenomas, with high sensitivity and specificity. This suggests it could be useful in diagnosing conditions like Cushing's Syndrome, where accurate localization of hormone-producing tumors is crucial. ^{1 2 3 4 5}

Is 68Ga-Pentixafor safe for use in humans?

68Ga-Pentixafor has been used safely in humans for imaging adrenal masses, showing potential as a non-invasive diagnostic tool. It is considered safe and readily available for outpatient procedures. ^{1 3 4 6 7}

How is the drug [68Ga]Ga-PentixaFor unique in treating Cushing's Syndrome?

[68Ga]Ga-PentixaFor is unique because it is a PET imaging tracer that helps in the non-invasive identification and characterization of adrenal masses, which can be crucial for diagnosing conditions like Cushing's Syndrome. Unlike traditional treatments, it offers a safer and more accessible alternative to invasive procedures like adrenal vein sampling, making it a novel diagnostic tool rather than a direct treatment for the syndrome. ^{1 2 3 4 6}

Research Team

Maria Liza Lindenberg, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for adults over 18 with adrenal tumors that produce excess hormones, specifically aldosterone or cortisol. Participants must also be part of other related NIH studies and have the ability to perform normal activities.

Inclusion Criteria

Breastfeeding should be discontinued for one week after the [68Ga]Ga-PentixaFor scan

I agree not to donate sperm for a week after my scan.

I agree to use effective birth control before and after my scan.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants will undergo a [68Ga]Ga-PentixaFor PET/CT or PET/MR scan to evaluate adrenal adenomas

1 day

1 visit (in-person)

Safety Follow-up

A safety visit will be performed 3 days following the [68Ga]Ga-PentixaFor imaging to monitor for adverse events

3 days

1 visit (in-person or virtual)

Long-term Follow-up

Participants will remain on-study for 1 year for correlative analysis and monitoring

1 year

Treatment Details

Interventions

• [68Ga]Ga-PentixaFor (Radiopharmaceutical)

Trial Overview [68Ga]Ga-PentixaFor, a new radioactive tracer, is being tested to see if it improves the detection of functional adrenal tumors using PET scans. Patients will undergo one scan after receiving the tracer intravenously.

Participant Groups

Group I: 1/[68Ga]Ga-PentixaFor PET/CT or PET/MR Experimental Treatment 1 Intervention

Participants will undergo \[68Ga\]Ga-PentixaFor PET/CT or PET/MR

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study analyzing 30 PET/CT scans from 18 patients suspected of having ectopic Cushing's syndrome, the tracers [68Ga]-DOTANOC and [18F]FDOPA demonstrated superior diagnostic capabilities compared to [18F]FDG, with [68Ga]-DOTANOC detecting tumors in all cases it was used.

Notably, [18F]FDOPA was the only tracer that did not produce any false positive results, indicating its potential as a reliable option for diagnosing ectopic Cushing's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome. Zisser, L., Kulterer, OC., Itariu, B., et al.[2021]

68Ga-Pentixafor PET/CT imaging effectively differentiates between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), showing a sensitivity of 87.7% and a specificity of 100% in a study of 85 patients.

The maximum standard uptake value (SUVmax) from the imaging correlates with key clinical factors such as lesion size and aldosterone/renin activity ratio, and it predicts better postoperative outcomes, with a higher complete remission rate in patients with positive imaging results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma]. Gao, YJ., Ding, J., Cui, YY., et al.[2023]

A new PET imaging method using the tracer [68Ga]Ga-PentixaFor shows promise for accurately diagnosing primary aldosteronism (PA) by distinguishing between aldosterone-producing adenomas and bilateral adrenal hyperplasia, potentially offering a safer and cheaper alternative to the invasive adrenal vein sampling (AVS).

The proposed study will assess the accuracy of [68Ga]Ga-PentixaFor PET/CT compared to AVS in a two-step randomized controlled trial, aiming to improve diagnostic outcomes and reduce the need for more complex procedures in patients with PA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS). Chaman Baz, AH., van de Wiel, E., Groenewoud, H., et al.[2022]

68Ga-pentixafor PET/CT imaging demonstrated high sensitivity (97.8%) and specificity (87.5%) for functional lateralization of adrenocortical lesions in a study of 64 patients with benign adrenal masses, indicating its effectiveness in diagnosing adrenal tumors.

The imaging technique also allowed for the differentiation between active and inactive adrenocortical adenomas, with specific SUVmax cutoffs providing high sensitivity and specificity, suggesting its potential as a noninvasive tool for characterizing adrenal masses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Characterization of Adrenocortical Masses in Nononcologic Patients Using 68Ga-Pentixafor. Ding, J., Tong, A., Zhang, Y., et al.[2022]

In a study of 28 patients with ectopic ACTH-secreting tumors (ECS), [68 Ga]-DOTATATE PET/CT successfully identified the suspected primary tumor in 65% of cases, leading to surgical intervention in many patients.

The imaging technique also significantly influenced clinical management, resulting in changes for 64% of patients evaluated during follow-up, highlighting its utility in detecting tumors that conventional imaging might miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours. Wannachalee, T., Turcu, AF., Bancos, I., et al.[2020]

GalLium-based (Ga68) somatostatin receptor analogs show better sensitivity for diagnosing bronchial carcinoids that cause ectopic Cushing syndrome, suggesting they may be a useful tool in identifying this specific source of excess cortisol.

FDG PET imaging is more effective for detecting small-cell lung cancers and other aggressive tumors associated with ectopic Cushing syndrome, highlighting the need for further research to determine the optimal PET tracer for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging in ectopic Cushing syndrome: a systematic review. Santhanam, P., Taieb, D., Giovanella, L., et al.[2022]

In a study of seven patients with Cushing's syndrome, 131I-19-iodocholesterol adrenal scans revealed distinct imaging patterns that helped differentiate between conditions like bilateral adrenal hyperplasia and adrenocortical tumors.

The scans demonstrated that this noninvasive imaging technique effectively identifies adrenal abnormalities, aiding in the diagnosis and treatment of Cushing's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scanning of the adrenals in Cushing's syndrome. Gogas, JG., Skalkeas, GD., Sechas, MN., et al.[2016]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome. [2021]

2. China pubmed.ncbi.nlm.nih.gov

[Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma]. [2023]

3. England pubmed.ncbi.nlm.nih.gov

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Functional Characterization of Adrenocortical Masses in Nononcologic Patients Using 68Ga-Pentixafor. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

PET imaging in ectopic Cushing syndrome: a systematic review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Scanning of the adrenals in Cushing's syndrome. [2016]