CapTem + Radioembolization for Liver Metastases from Neuroendocrine Tumors

(CapTemY90 Trial)

Overseen By Kathleen Thomas, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active infection, Heart failure, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or intolerable toxicities

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with grade 2 neuroendocrine tumors that have spread to the liver and cannot be surgically removed. The treatment combines two drugs, capecitabine and temozolomide, with a targeted radiation therapy called yttrium-90 radioembolization (also known as SIR-Spheres). The trial aims to evaluate the effectiveness of this combined approach in controlling the disease. Suitable candidates have neuroendocrine tumors primarily affecting their liver, with at least one sizable tumor (over 1 cm) in the liver. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have at least 4 weeks since your last chemotherapy or radiotherapy treatment before joining the trial.

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

Research shows that combining capecitabine and temozolomide with yttrium-90 radioembolization (a type of radiation treatment) is safe and feasible for people with liver tumors from neuroendocrine cancer. Studies have found that while these treatments can cause combined side effects, they are usually manageable. This means side effects can occur, but they can be controlled.

Earlier studies demonstrated that using capecitabine and temozolomide with radioembolization effectively controlled the cancer. The treatment exceeded expectations, providing good disease control. Previous research on radioembolization alone also showed high rates of disease control, with improvements in symptoms and quality of life for patients.

Overall, these treatments have shown promise in being safe and effective, offering hope for better outcomes in managing liver tumors from neuroendocrine cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Capecitabine and Temozolomide with radioembolization for liver metastases from neuroendocrine tumors because it offers a unique approach compared to standard treatments like surgery, chemotherapy, or targeted therapies. This treatment uses Y-90 radioembolization, which directly targets liver tumors with radiation, potentially sparing more healthy tissue. Additionally, Capecitabine and Temozolomide, known for their oral administration and manageable side effects, complement the precise action of radioembolization. This combination could lead to more effective tumor control while minimizing overall toxicity, offering hope for improved outcomes in patients with this challenging condition.

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

In this trial, participants will receive a combination of two drugs, capecitabine and temozolomide, along with yttrium-90 radioembolization. Research has shown that this combination can effectively treat cancer that has spread to the liver from neuroendocrine tumors. Studies have found it safe and feasible, with patients responding better than expected and achieving good disease control. Specifically, patients with grade 2 neuroendocrine tumors have experienced positive results, indicating that these treatments work well together. This evidence supports the potential effectiveness of this treatment in managing the condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Soulen, MD

Principal Investigator

University of Pennsylvania Abramson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with grade 2 neuroendocrine tumors and liver metastases that can't be removed by surgery. Participants need measurable liver disease, at least half of their tumor burden in the liver, proper organ function, and no recent treatments. They must not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

You are expected to live for at least 6 more months.

I have a grade 2 neuroendocrine tumor with liver metastases that cannot be surgically removed.

Exclusion Criteria

Patients may not be receiving any other investigational agents

I cannot take capecitabine or temozolomide due to health reasons.

Pregnant and lactating women are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Capecitabine and Temozolomide (CapTem) with Yttrium-90 radioembolization. Capecitabine is given for 14 days and Temozolomide on days 10-14 of the cycle. Y-90 radioembolization is performed on Day 7 of the 2nd and possibly 3rd or 4th cycles.

Until disease progression or intolerable toxicities

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• SIR-Spheres
• Temozolomide

Trial Overview The study tests a combination of Capecitabine and Temozolomide tablets with SIR-Spheres radioembolization to treat liver metastases from neuroendocrine tumors. It's a Phase 2 trial aiming to confirm the effectiveness of this integrated chemoradiation approach.

How Is the Trial Designed?

Group I: CapTemY90 Experimental Treatment 1 Intervention

Capecitabine 600 mg/m2 twice daily for 14 days and temozolomide 150-200 mg/m2 in two divided doses on Days 10-14, with 14 days between cycles, to be continued until 1) disease progression or 2) intolerable toxicities. During the initial cycle of CapTem, simulation angiography for Y-90 radioembolization planning will be performed. Once the patient has successfully completed the first cycle of CapTem and undergone simulation demonstrating eligibility for Y-90 radioembolization, the dominant lobe will be treated on Day 7 of the 2nd cycle of CapTem. Resin microspheres will be prescribed according to the BSA method per the manufacturer's Instructions for Use. If the other hepatic lobe needs to be treated, this will be done on Day 7 of the 3rd or 4th cycle of CapTem.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

CARTI

Collaborator

Trials

3

Recruited

610+

Published Research Related to This Trial

In a study of 18 patients with metastatic neuroendocrine tumors (NETs) to the liver, the combination of capecitabine and temozolomide (CAPTEM) showed a total response rate of 61%, with 1 patient achieving a complete response and 10 achieving a partial response.

CAPTEM was well tolerated, with only 11% of patients experiencing grade 3 thrombocytopenia and no severe toxicities, suggesting it is a safe treatment option that may prolong survival in patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience. Fine, RL., Gulati, AP., Krantz, BA., et al.[2022]

The integrated treatment protocol of capecitabine-temozolomide with yttrium-90 radioembolization (CapTemY90) was found to be feasible and safe for patients with unresectable grade 2 neuroendocrine tumors, with 19 out of 21 patients completing the treatment without unexpected adverse events.

The treatment showed promising efficacy, achieving a 74% objective response rate in the liver and a 67% progression-free survival rate at 3 years, indicating potential synergistic effects in controlling liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 Liver-Dominant Metastatic Neuroendocrine Tumors. Soulen, MC., van Houten, D., Teitelbaum, UR., et al.[2019]

A systematic review of 42 articles involving 1818 patients showed that the combination of capecitabine and temozolomide (CAPTEM) achieved a high disease control rate of 77% in treating neuroendocrine tumors (NENs).

The treatment demonstrated a median progression-free survival of 4 to 38.5 months and a median overall survival of 8 to 103 months, with manageable safety profiles, as severe toxicities occurred in 16.4% of patients, primarily hematological.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. Arrivi, G., Verrico, M., Roberto, M., et al.[2023]

In a study of 79 patients with advanced neuroendocrine neoplasms (NENs), the combination of capecitabine and temozolomide (CAPTEM) showed a partial response rate of 29.1% and a median progression-free survival of 10.1 months, indicating its effectiveness in treating these tumors.

The safety profile of CAPTEM was favorable, with only rare serious toxicities reported and low discontinuation rates, suggesting that it can be administered safely even for prolonged periods (up to 55.6 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms. Chatzellis, E., Angelousi, A., Daskalakis, K., et al.[2020]

In a study of 308 patients with metastatic neuroendocrine tumors treated with capecitabine plus temozolomide (CAPTEM), first-line treatment showed significantly better outcomes, with a median progression-free survival of 16.1 months and overall survival of 105.8 months compared to later lines of treatment.

The treatment was generally well-tolerated, with only 22.5% of patients experiencing severe side effects (grade 3-4), and a low discontinuation rate of 9.5%, indicating that CAPTEM is a safe and effective option for managing metastatic NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group. Ünal, Ç., Azizy, A., Karabulut, S., et al.[2023]

A review of 5,127 reports on temozolomide (TMZ) revealed 112 cases of major hematologic adverse events (HAEs), with a significant number of these cases leading to death, highlighting the serious risks associated with this medication.

Aplastic anemia (AA) and leukemia were the most common major HAEs linked to TMZ, indicating a unique toxicity profile compared to other alkylating agents, and suggesting that patients should be informed about these risks, especially since AA can develop after a short duration of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic adverse events associated with temozolomide. Villano, JL., Letarte, N., Yu, JM., et al.[2018]

In a study involving 37 patients with grade 2 neuroendocrine tumor (NET) liver metastases, the combination of Capecitabine-Temozolomide (CapTem) and Y90 transarterial radioembolization (TARE) achieved a high objective response rate of 72% and a disease control rate of 100%.

The median progression-free survival was 36 months and median overall survival was 41 months from the start of treatment, indicating that this combined therapy offers durable control of liver metastases significantly longer than expected with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated Capecitabine-Temozolomide with Radioembolization for Liver-Dominant G2 NETs: Long-Term Outcomes of a Single-Institution Retrospective Study. Soulen, MC., Teitelbaum, UR., Mick, R., et al.[2023]

The CAPTEM regimen shows a high efficacy in treating advanced neuroendocrine tumors (NETs), with a 46% objective response rate and a median progression-free survival of 18 months, particularly effective in well-differentiated pancreatic NETs.

The treatment is exceptionally safe, with low incidences of severe myelotoxicity (grade 4 thrombocytopenia at 7% and neutropenia at 3%), and a negligible risk of opportunistic infections like Pneumocystis pneumonia, suggesting that sex-based dosing may be beneficial due to higher toxicity rates in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms. Al-Toubah, T., Pelle, E., Valone, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04339036

CapTemY90 for Grade 2/3 NET Liver Metastases This is a Phase 2 evaluation of hepatic-progression free survival among patients with Grade 2 liver-dominant NET metastases undergoing combination therapy ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30028446/

Safety and Feasibility of Integrating Yttrium-90 ... CapTemY90 is feasible and safe for grade 2 NETs. Toxicities were additive. Oncologic outcomes suggest synergy.

3. endocrine-abstracts.org endocrine-abstracts.org/ea/0108/ea0108c29

Initial outcomes of integrating yttrium-90 radioembolization ... Embolotherapy of G3 hepatic metastases has poor outcomes with median hepatic progression free survival (HPFS) of 4.9 months and overall survival (OS) of 9.3 ...

4. nanets.net nanets.net/abstracts-archive/2024/2067-c29-d-souza-integrating-yttrium-90-radioembolization-with-capecitabine-temozolomide-for-grade-3-liver-dominant-metastatic-neuroendocrine-tumors-initial-outcomes/file

Integrating Yttrium - 90 Radioembolization with Capecitabine Grade 3 Liver-Dominant Metastatic Neuroendocrine Tumors: Initial Outcomes ... Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 ...

5. researchgate.net researchgate.net/publication/326502071_Safety_and_Feasibility_of_Integrating_Yttrium-90_Radioembolization_With_Capecitabine-Temozolomide_for_Grade_2_Liver-Dominant_Metastatic_Neuroendocrine_Tumors

Safety and Feasibility of Integrating Yttrium-90 ... This report describes the feasibility and safety of this regimen. Methods: Twenty-one patients with unresectable grade 2 NET liver-dominant metastases without ...

6. jvir.org jvir.org/article/S1051-0443(13)02211-2/fulltext

Feasibility of combining capecitabine and temozolomide ... We investigated the safety and tolerability of combining CapTem with Y90 radioembolization for progressive Grade 2 NETs with liver-dominant metastases.

7. eo.bioscientifica.com eo.bioscientifica.com/view/journals/eo/5/1/EO-24-0053.xml

Radioembolization for neuroendocrine tumors: procedure ... Radioembolization is effective as a standalone treatment. This treatment achieves disease control rates exceeding 90% and improves symptoms and quality of life.

8. nature.com nature.com/articles/bjc2014344

Phase I study of capecitabine combined with ... Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.