Sunitinib + Lutathera for Pancreatic Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Heart failure, Stroke, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

Duration: 32 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and optimal dose of combining sunitinib malate and lutetium Lu 177 dotatate for patients with pancreatic neuroendocrine tumors. Sunitinib malate slows the spread of cancer cells, while lutetium Lu 177 dotatate delivers targeted radiation to kill tumor cells. Participants should have pancreatic neuroendocrine tumors that cannot be surgically removed and have shown some growth despite treatment. This combination might prove more effective than using either treatment alone. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong CYP3A4 inhibitors or inducers close to the start of the trial. It's important to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining sunitinib malate and lutetium Lu 177 dotatate is under investigation for potential benefits in treating pancreatic neuroendocrine tumors. Previous studies have found that lutetium Lu 177 dotatate is generally well-tolerated, with manageable side effects. It targets tumor cells directly, helping to protect normal cells. Sunitinib malate, already approved by the FDA for other cancers, is known to be safe when used alone, blocking proteins that aid tumor growth.

Using these treatments together might enhance effectiveness. Although this trial is in its early stages and primarily focuses on safety, existing data suggests both treatments are generally well-tolerated individually. However, the safety of their combined use is still under study. This trial aims to determine the best dose while closely monitoring for side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pancreatic cancer because it combines two innovative approaches: Lutetium Lu 177 dotatate, a targeted radioligand therapy, and Sunitinib Malate, a tyrosine kinase inhibitor. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Lutetium Lu 177 dotatate specifically targets cancer cells with a radioactive isotope, potentially reducing side effects. Sunitinib Malate further enhances this effect by blocking pathways that tumors use to grow and spread. This dual-action strategy could offer a more precise and effective treatment option compared to current standards like gemcitabine or FOLFIRINOX.

What evidence suggests that this trial's treatments could be effective for pancreatic neuroendocrine tumors?

Research suggests that using sunitinib malate and lutetium Lu 177 dotatate together, as studied in this trial, might treat pancreatic neuroendocrine tumors more effectively than using each drug alone. Sunitinib malate blocks proteins that help tumors grow, while lutetium Lu 177 dotatate delivers radiation directly to tumor cells to kill them. Studies have shown that lutetium Lu 177 dotatate can help slow cancer progression in patients with advancing neuroendocrine tumors. Although using sunitinib malate or lutetium Lu 177 dotatate alone hasn't shown strong results, combining them might enhance effectiveness. This approach aims to target tumor cells more precisely and reduce damage to normal cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Nikolaos Trikalinos

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with well- or moderately-differentiated pancreatic neuroendocrine tumors that are metastatic/unresectable, who have had up to one line of systemic therapy (excluding somatostatin analogs), and can swallow pills. They must not be pregnant, agree to use contraception, and have adequate organ function. Excluded are those with certain heart conditions, uncontrolled illnesses, recent serious cardiovascular events, or prior treatment with similar drugs.

Inclusion Criteria

My hepatitis B is under control with treatment.

I can take care of myself but might not be able to do heavy physical work.

My heart function is classified as class 2B or better according to the NYHA.

Exclusion Criteria

You are currently taking any other experimental medications.

You cannot participate if you have certain health conditions like serious wounds, history of specific heart or blood vessel issues, uncontrolled illness, or if you are pregnant or breastfeeding.

I am allergic to medications similar to sunitinib malate or lutetium Lu 177 dotatate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive sunitinib malate orally daily and lutetium Lu 177 dotatate intravenously on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles.

32 weeks

4 visits (in-person) for lutetium Lu 177 dotatate administration, additional visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Extension

Optional continuation of treatment for further monitoring and assessment of long-term outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Dotatate
• Sunitinib Malate

Trial Overview The trial is testing the combination of Sunitinib Malate (a kinase inhibitor) and Lutetium Lu 177 Dotatate (a radioactive drug targeting tumor cells) for safety and effectiveness in treating pancreatic neuroendocrine tumors. It's a phase I study determining the best dose while monitoring side effects.

How Is the Trial Designed?

Group I: Treatment (sunitinib malate, lutetium Lu 177 dotatate) Experimental Treatment 6 Interventions

Patients receive sunitinib malate PO QD from day 1 of lutetium 177 dotatate therapy to 28 days after the last dose of lutetium 177 dotatate in the absence of unacceptable toxicity. Patients also receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat Q8W for 4 cycles in the absence of unacceptable toxicity. Patients undergo a CT scan and/or MRI throughout the trial. Patients also undergo a SSR PET/CT scan during screening and blood sample collection on study.

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

Approved in European Union as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Approved in United States as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

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

The combination of Lutathera and nivolumab was well tolerated in a phase I study involving nine patients with advanced neuroendocrine tumors, with no dose-limiting toxicities observed at the lower dose level.

This treatment showed preliminary signs of antitumor activity, including a partial response in one patient with extensive-stage small cell lung cancer and stable disease in two patients with pulmonary atypical carcinoid, suggesting potential for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. Kim, C., Liu, SV., Subramaniam, DS., et al.[2021]

Lutetium Dotatate (Lutathera) is an FDA-approved radiopharmaceutical therapy for treating somatostatin receptor positive neuroendocrine tumors, allowing for effective outpatient treatment.

The study confirms that Lutathera can be safely administered on an outpatient basis, provided that patients are informed about safety measures and travel restrictions related to radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Release and Instructions for Lutetium Dotatate Radiopharmaceutical Therapy. Underwood, J., Sturchio, G., Arnold, S.[2023]

Sunitinib malate is a small molecule kinase inhibitor effective against various tyrosine kinase receptors and has recently been approved for treating advanced pancreatic neuroendocrine tumors, in addition to its existing approvals for renal cell carcinoma and gastrointestinal stromal tumors.

The use of sunitinib in treating rare tumors like peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL), and epithelioid hemangioendothelioma (EHE) is promising due to these tumors' overexpression of pro-angiogenic factors, suggesting that sunitinib may help manage these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports. Prochilo, T., Savelli, G., Bertocchi, P., et al.[2022]

In a study of 219 Lutathera injections over 70 months, using a peristaltic pump (method 2) resulted in a 34.9% reduction in residual radioactivity compared to a volumetric infusion pump (method 1), indicating improved efficiency in drug delivery.

Despite method 2 having a higher cost per injection, it was reported to be safer and more suitable by operators, with no major incidents occurring during its use, suggesting it may be a better option for future radioligand therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods. Donzé, C., Rubira, L., Santoro, L., et al.[2022]

In a study of 110 patients with advanced pancreatic neuroendocrine tumors (panNETs), treatment with 177Lu-DOTATATE resulted in a median progression-free survival (PFS) of 24.8 months and an overall survival (OS) of 41.4 months, indicating its efficacy in managing this type of cancer.

The treatment was well-tolerated, with no serious adverse events leading to discontinuation, and only a small percentage of patients experiencing grade 3 side effects, suggesting a favorable safety profile for 177Lu-DOTATATE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of 177Lu‑DOTATATE in patients with advanced pancreatic neuroendocrine tumours: data from the NETTER-R international, retrospective study. Clement, D., Navalkissoor, S., Srirajaskanthan, R., et al.[2022]

Lutathera® is the first approved radiopharmaceutical for radioligand therapy, specifically indicated for adult patients with progressive unresectable somatostatin receptor-positive gastroenteropancreatic neuroendocrine neoplasms, based on the NETTER1 trial.

Despite its approval, patients with SSTR-positive tumors from other regions and those with well-differentiated G3 GEP-NET are currently excluded from treatment, highlighting a gap in access to Lutathera® and the need for further research and clinical trials to explore its efficacy in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE. Urso, L., Nieri, A., Uccelli, L., et al.[2023]

In a phase II study involving 47 patients with advanced non-small cell lung cancer (NSCLC), sunitinib showed a low objective response rate of 2.1%, but 23.4% of patients experienced stable disease for at least 8 weeks, indicating some potential for disease control.

The treatment was generally well tolerated, with a median progression-free survival of 11.9 weeks and a median overall survival of 37.1 weeks, suggesting that sunitinib may be a viable option for patients who have not responded to platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Novello, S., Scagliotti, GV., Rosell, R., et al.[2021]

Sunitinib malate was approved by the FDA for treating progressive pancreatic neuroendocrine tumors (pNETs) based on a phase III trial involving 171 patients, showing a median progression-free survival of 10.2 months compared to 5.4 months for placebo.

Despite some concerns about the early termination of the trial potentially overestimating treatment effects, the Oncologic Drugs Advisory Committee and the FDA concluded that sunitinib has a favorable benefit-risk profile, although it is associated with common adverse reactions like diarrhea, fatigue, and serious risks such as cardiac failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors. Blumenthal, GM., Cortazar, P., Zhang, JJ., et al.[2021]

In a study of eight patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who had relapsed on standard therapy, sunitinib malate showed promising efficacy, with three patients achieving partial remission and five experiencing disease stabilization, leading to a median progression-free survival of 11 months.

Sunitinib was generally well-tolerated, with adverse effects such as leukopenia and anemia occurring in 25% of patients, and mucocutaneous lesions in 37.5%, but these did not worsen with concurrent somatostatin analogues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the safety and efficiency of sunitinib malate in metastatic neuroendocrine tumours of the pancreas (NEN G1/G2) depending on the number and type of earlier therapeutic lines - initial report. Wachuła, E., Ćwikła, JB., Rogowski, W., et al.[2018]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

Sunitinib malate is an oral medication that inhibits key pathways involved in tumor growth and blood vessel formation, making it a potential treatment for metastatic breast cancer.

In a report involving four patients with advanced breast cancer, combining sunitinib with docetaxel chemotherapy led to clinically meaningful responses, suggesting that this combination may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early experience with sunitinib, combined with docetaxel, in patients with metastatic breast cancer. Liljegren, A., Bergh, J., Castany, R.[2018]

SU11248 (sunitinib) effectively sensitizes pancreatic cancer cells to ionizing radiation, significantly reducing their survival rates after treatment, as shown in both in vitro and in vivo studies.

When combined with radiation, SU11248 delayed tumor growth in mice by 30 days, indicating its potential to enhance the efficacy of radiation therapy in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SU11248 (sunitinib) sensitizes pancreatic cancer to the cytotoxic effects of ionizing radiation. Cuneo, KC., Geng, L., Fu, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05687123

NCT05687123 | Testing the Addition of Sunitinib Malate to ... Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/391061

Testing the Addition of Sunitinib Malate to Lutetium Lu 177 ... Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/lutetium-lu-177-dotatate?pn=1

Clinical Trials Using Lutetium Lu 177 Dotatate - NCI Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors. Status: Active. Location: 7 locations.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38109041/

Sunitinib in Tandem With 177 Lu-DOTATATE Therapy ... We present a case of 40-year-old man with advanced pancreatic NET where PRRT or sunitinib as monotherapy had a suboptimal treatment response.

5. onclive.com onclive.com/view/lutathera-improves-pfs-in-progressive-neuroendocrine-pancreatic-tumors

Lutathera Improves PFS in Progressive Neuroendocrine ... Lutathera improved progression-free survival (PFS) in patients with unresectable, progressive neuroendocrine pancreatic tumors, according to data from the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12089376/

Emerging innovations in theranostics for pancreatic ... The rationale for combining sunitinib with 177Lu-DOTATATE is based on its ability to enhance the tumor vasculature and oxygenation, possibly ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/5/746

Effectiveness and Safety of Retreatment with 177Lu ... Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1393317/full

Long-term clinical outcomes of [ 177 Lu]Lu-DOTATATE in ... Treatment was overall well tolerated, and the safety profile was consistent with published data. The role of tumor grade and non-ileal ...