Lutathera for Pheochromocytoma/Paraganglioma

Overseen By Joy H Zou, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Somatostatin analogues

Must not be taking: Antidepressants

Disqualifiers: Liver dysfunction, Brain metastases, 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: 17

Duration: 32 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Lu-177-DOTATATE, a type of targeted radiotherapy, for individuals with pheochromocytoma or paraganglioma. These rare tumors can form near the adrenal gland or in the neck. The trial aims to determine if this treatment is safe and can delay cancer recurrence in cases where tumors cannot be surgically removed. Participants must have a tumor visible on a Ga-68-DOTATATE PET/CT scan and be ineligible for surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on somatostatin analogue therapy, it should not be started or changed within 3 months of joining the study. If you are on short-term octreotide, you may need to pause it for 24 hours before receiving the study drug.

Is there any evidence suggesting that Lu-177-DOTATATE is likely to be safe for humans?

Research has shown that Lu-177-DOTATATE, also known as Lutathera, is generally well-tolerated in studies on neuroendocrine tumors. A review of these studies found that this treatment is safe for patients. Other research suggests that patients usually handle it well, even in advanced tumor stages.

In a specific study of patients with metastatic pheochromocytoma and paraganglioma, Lu-177-DOTATATE proved to be very effective and safe. This indicates that the treatment works well for certain tumors and is also safe for patients.

While some side effects can occur, as with any treatment, evidence suggests that most patients manage them well. Discussing any concerns with healthcare providers before joining a trial is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pheochromocytoma/paraganglioma, which often involve surgery, chemotherapy, or external beam radiation, Lu-177-DOTATATE offers a targeted approach. This treatment uses a radioactive particle, Lu-177, linked to a molecule that specifically seeks out and binds to tumor cells, delivering radiation directly to them and sparing healthy tissue. Researchers are excited because this precision not only promises fewer side effects but also potentially improved effectiveness. Additionally, its method of direct delivery every eight weeks is convenient compared to some existing therapies, potentially improving patient quality of life.

What evidence suggests that Lu-177-DOTATATE might be an effective treatment for pheochromocytoma/paraganglioma?

Research has shown that Lu-177-DOTATATE, the treatment under study in this trial, may help treat advanced tumors such as pheochromocytoma and paraganglioma. In one study, patients who received this treatment had their cancer remain stable for nearly 20 months. Another study found that about 89% of patients experienced positive results, indicating that the treatment can effectively control tumor growth. Lu-177-DOTATATE targets tumor cells with radiation, which can shrink tumors and slow disease progression. This treatment might offer hope for individuals with tumors that cannot be surgically removed. ^{1 2 3 6 7}

Who Is on the Research Team?

Frank I Lin, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with inoperable pheochromocytoma or paraganglioma that shows up on a Ga-68-DOTATATE PET/CT scan. They should have progressive disease, no severe liver or kidney issues, and not be pregnant. Participants must agree to use non-hormonal contraception for 6 months post-treatment if of childbearing potential.

Inclusion Criteria

Negative serum pregnancy test for women of childbearing potential

Agreement to use effective, non-hormonal contraception

Must have outside endocrinologist/medical oncologist who can follow the participant after receiving PRRT (NIH only requirement)

Exclusion Criteria

Pregnancy or lactation

Patient weight > 400 lbs

Participation in any therapeutic clinical study with an investigational agent within the last 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Lu-177-DOTATATE via intravenous infusion every 8 weeks for a total of 4 doses

32 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 12 weeks until 3 years after the first administration

3 years

Remote or telemedicine visits every 12 weeks

Long-term follow-up

Participants are contacted yearly to assess survival and disease status after the initial 3-year follow-up period

Until death

What Are the Treatments Tested in This Trial?

Interventions

• Lu-177-DOTATATE

Trial Overview The trial is testing Lu-177-DOTATATE's safety and effectiveness against rare tumors near the adrenal gland or neck region. Patients receive four intravenous doses about eight weeks apart, followed by scans and regular check-ups including quality of life assessments over three years.

How Is the Trial Designed?

Group I: 1/Lu-177-DOTATATE Experimental Treatment 4 Interventions

Lu-177-DOTATATE is administered IV every 8 (+/- 2) weeks, for a total of 4 administrations. A Ga-68-DOTATATE PET and F-18-FDG-PET, as well as CT/ MRI for RECIST monitoring, will be obtained post 2 administrations and post 4 administrations. Concomitant administration of an IV infusion of an amino acid (AA) solution will also be done for renal protection. Concomitant administration of an IV infusion of an amino acid (AA) solution will also be done for renal protection.

Lu-177-DOTATATE is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults

Approved in United States as Lutathera for:

• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults and children aged 12 years and older

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

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

The study developed and validated a high-performance liquid chromatography (HPLC) method for quality control of the radiopeptide [177Lu]Lu-DOTA-TATE, ensuring its radiochemical purity meets therapeutic standards (95-105% of label claim).

The HPLC method demonstrated accuracy, precision, and sensitivity, making it suitable for clinical samples, which is crucial for the safe and effective use of [177Lu]Lu-DOTA-TATE in treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. van Andel, L., Aalbersberg, EA., Geluk-Jonker, MM., et al.[2021]

[177Lu]Lu-DOTA-TATE shows promising antitumor activity in treating advanced somatostatin receptor-positive tumors, including pheochromocytoma/paraganglioma and bronchial neuroendocrine tumors, based on a systematic review of 16 studies.

The treatment is generally safe, with most side effects being mild to moderate and transient, similar to those observed in patients with gastroenteropancreatic neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review. Hertelendi, M., Belguenani, O., Cherfi, A., et al.[2023]

Lutathera, approved in Japan in 2021, is the first peptide receptor radionuclide therapy specifically designed for treating somatostatin receptor-positive neuroendocrine tumors, providing a much-needed treatment option for these patients.

Current imaging methods in Japan for assessing somatostatin receptor expression in tumors primarily rely on In-111 pentetreotide scintigraphy, but advancements like 68Ga-DOTA-SSA PET/CT are being explored to improve evaluation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors]. Koyasu, S., Shimizu, Y., Nakamoto, Y.[2022]

In a study involving seven patients with neuroendocrine tumors, the peptide [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE) demonstrated a longer residence time in tumors compared to [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC), suggesting it may be more effective for peptide receptor radionuclide therapy (PRRT).

Although (177)Lu-DOTATATE resulted in longer residence times in the kidneys, the overall tumor dose was still higher, making (177)Lu-DOTATATE the preferred choice for PRRT despite potential kidney dose concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Esser, JP., Krenning, EP., Teunissen, JJ., et al.[2019]

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, M., et al.[2023]

The development of a single vial kit for (177) Lu-DOTATATE allows for safe and efficient preparation of this radiopharmaceutical in hospital settings, making it more accessible for treating patients with inoperable neuroendocrine tumors.

Preclinical studies showed that (177) Lu-DOTATATE is rapidly cleared from the body through the kidneys, indicating a favorable biodistribution profile that supports its use in peptide receptor radionuclide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. Mukherjee, A., Lohar, S., Dash, A., et al.[2019]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

177Lu-octreotate therapy showed potential effectiveness in treating paragangliomas and meningiomas, with some patients experiencing tumor regression or stable disease, although response rates were lower than in gastroenteropancreatic neuroendocrine tumors.

The treatment did not demonstrate any antitumor effects in patients with small cell lung carcinoma or melanoma, highlighting the need for further studies to confirm these findings due to the small patient sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. van Essen, M., Krenning, EP., Kooij, PP., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10135775/

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with ... Background: We have performed a systematic review to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03206060

NCT03206060 | Lu-177-DOTATATE (Lutathera) in Therapy ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/p1296

Safety and Efficacy of Lu-177-DOTATATE in Metastatic or ... Results: For the interim analysis, 36 patients (18 per cohort) were evaluated for safety and efficacy. For the sporadic cohort, 16 (89%) patients achieved ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12367064/

Phase 2 Study of 177Lu-DOTATATE for Progressive ... In the assessment of treatments for PPGL supported by prospective data, 177Lu-DOTATATE demonstrates a favorable efficacy profile with a reported PFS of 19.9 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.TPS4159

Phase 2 trial of Lu-177-DOTATATE in inoperable ... This is a prospective, single center, open label Phase 2 study evaluating the efficacy of Lu-177-DOTATATE in PHEO/PGL.

6. asco.org asco.org/abstracts-presentations/ABSTRACT263553

Phase 2 trial of Lu-177-DOTATATE in inoperable ... Phase 2 trial of Lu-177-DOTATATE in inoperable pheochromocytoma/paraganglioma. · Author Details · Frank Lin · Abstract Details.

7. hhs.iowa.gov hhs.iowa.gov/media/400/download?inline

Lutathera (lutetium Lu 177 dotatate) Lutathera® is considered medically necessary when ALL of the following are met: 1. Diagnosis of pheochromocytoma or paraganglioma and disease is.