Radioactive Tracer for Cushing's Syndrome

Overseen By Yolanda L McKinney, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Uncontrolled illness, MRI contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better methods to determine if adrenal tumors are functional, meaning they release hormones. Researchers are testing a new radioactive tracer, [68Ga]Ga-PentixaFor, to identify these tumors using PET scans. The trial includes individuals with adrenal tumors and increased hormone levels who are already part of certain NIH studies. Participants will receive a PET scan after receiving the tracer, which will help capture clear images of the tumors. This study could lead to more accurate diagnoses and improved treatment plans for those with adrenal tumors. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in diagnosing adrenal tumors.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the treatment using the radioactive tracer [68Ga]Ga-PentixaFor is generally safe for people. Studies have found that this tracer benefits patients with conditions affecting hormone levels, such as Cushing's syndrome, by helping identify adrenal tumors that release hormones.

Previous studies have not reported major side effects, indicating the tracer's safety for imaging scans. Participants in these studies did not experience serious side effects, and the procedure uses standard imaging methods. The tracer is injected into the bloodstream, and the scan captures detailed images of the adrenal glands.

While research is ongoing, current data supports [68Ga]Ga-PentixaFor as a safe choice for patients needing detailed imaging to diagnose hormone-related adrenal issues. Patients should always consult a healthcare professional to learn more about the treatment and its possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about [68Ga]Ga-PentixaFor for Cushing's Syndrome because it offers a novel way to pinpoint the condition using a radioactive tracer. While most current treatments for Cushing's Syndrome focus on managing symptoms or reducing excess cortisol production, this investigational approach targets precise imaging of the adrenal glands and other tissues involved. The unique mechanism of action involves using the radioactive tracer to enhance PET/CT or PET/MR scans, potentially allowing for more accurate diagnosis and assessment of the syndrome. This method could lead to earlier detection and better-targeted treatments, offering hope for improved management of the condition.

What evidence suggests that this radioactive tracer is effective for identifying functional adrenal tumors?

Research has shown that the new radioactive tracer, [68Ga]Ga-PentixaFor, holds promise for identifying functional adrenal tumors. One study demonstrated its effectiveness in aiding doctors' decisions for 20 patients with primary aldosteronism, with a success rate of 90%. This trial will evaluate [68Ga]Ga-PentixaFor's effectiveness in detecting hormone-producing tumors in various types of Cushing's Syndrome using PET scans. These findings suggest that [68Ga]Ga-PentixaFor could simplify the process for doctors to see and diagnose hormone-related adrenal tumors. ^{1 5 6 7 8}

Who Is on the Research Team?

Maria Liza Lindenberg, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [68Ga]Ga-PentixaFor

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.

How Is the Trial Designed?

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

[68Ga]Ga-PentixaFor is already approved in European Union, United States for the following indications:

Approved in European Union as 68Ga-Pentixafor for:

• Imaging of CXCR4 expression in tumors
• Detection of myeloproliferative neoplasms

Approved in United States as [68Ga]Ga-PentixaFor for:

• Investigational use in clinical trials for imaging of adrenal tumors
• Detection of myeloproliferative neoplasms

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11224210/

Clinical value of 68Ga-pentixafor PET/CT in patients with ... The lateralization results of 68Ga-pentixafor PET/CT supported the clinical decisions of 20 patients with PA, 90% of whom showed effectiveness ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35452014/

Usefulness of 68 Ga-Pentixafor PET/CT on Diagnosis and ... We have characterized the performance of 68 Ga-pentixafor in different subtypes of CS. 68 Ga-pentixafor PET/CT is promising in the ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251503

Diagnostic Utility of 68Ga-Pentixafor PET/CT in ACTH ... 2022. 68Ga-DOTANOC PET/CT in patients with Ectopic Cushing syndrome - evaluation of diagnostic efficacy and role in management. Bhagwant ...

4. researchgate.net researchgate.net/publication/360141561_Usefulness_of_68Ga-Pentixafor_PETCT_on_Diagnosis_and_Management_of_Cushing_Syndrome

Usefulness of 68Ga-Pentixafor PET/CT on Diagnosis and ... Results: Patients with Cushing disease characterized a focal uptake in adrenocorticotropic hormone-producing pituitary adenoma (ACTH-PA). In ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/cen.15204

Clinical Utility of Dual-Time 68 Ga-Pentixafor PET/CT in ... This study aimed to compare the clinical efficacy of dual-time 68Ga-pentixafor PET/CT with adrenal vein sampling (AVS) in PA lateralization.

6. jnm.snmjournals.org jnm.snmjournals.org/content/63/supplement_2/2363

Clinical Impact of 68Ga-pentixafor PET/CT on Diagnosis and ... NFAAs showed negative 68Ga-pentixafor signal. Patients with Cushing's disease characterized a focal uptake in ACTH-producing pituitary adenoma.

7. trialx.com trialx.com/clinical-trials/listings/297970/evaluating-the-functional-status-of-the-adrenal-glands-with-68gaga-pentixafor-in-hyperaldosteronism-and-hypercortisolism/?&radius=10&place=All%20Participating%20Sites&user_country=Germany

Evaluating the Functional Status of the Adrenal Glands ... [68Ga]Ga-PentixaFor may be useful in the evaluation of adrenal adenomas in the setting of Conn s or Cushing s syndrome. Localizing functional ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06125028

[68Ga]Ga-PentixaFor-PET Imaging for Staging of Marginal ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...