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

Trial Summary

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.

What data supports the effectiveness of the CapTem + Radioembolization treatment for liver metastases from neuroendocrine tumors?

Research shows that the combination of capecitabine and temozolomide (CapTem) is effective in treating neuroendocrine tumors (NETs), with high response rates and safety in patients. Additionally, integrating CapTem with Y90 radioembolization has shown promising results in improving response rates and progression-free survival in patients with liver metastases from NETs. ^{1 2 3 4 5}

Is the CapTem and radioembolization treatment generally safe for humans?

The combination of capecitabine and temozolomide (CapTem) has been studied for safety in patients with neuroendocrine tumors, showing some risk of severe blood-related side effects. The addition of radioembolization (a treatment that delivers radiation directly to the liver) has been evaluated in a feasibility study, indicating it is generally safe, but more research is needed to fully understand rare toxicities. ^{2 4 5 6 7}

What makes the CapTem + Radioembolization treatment unique for liver metastases from neuroendocrine tumors?

This treatment combines oral chemotherapy drugs, capecitabine and temozolomide, with yttrium-90 radioembolization, which targets liver tumors directly. The combination aims to enhance the effectiveness of treatment by using both drugs as radiosensitizers, potentially improving response rates and disease control in the liver compared to standard treatments. ^{1 2 5 7 8}

What is the purpose of this trial?

This trial tests a new treatment combining two chemotherapy drugs with targeted radiation for patients with grade 2 neuroendocrine tumors in the liver. The goal is to see if this combination is more effective and safer than current treatments. Early results suggest it could control the disease better with manageable side effects.

Research Team

Michael Soulen, MD

Principal Investigator

University of Pennsylvania Abramson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group. [2023]

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

Integrated Capecitabine-Temozolomide with Radioembolization for Liver-Dominant G2 NETs: Long-Term Outcomes of a Single-Institution Retrospective Study. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Hematologic adverse events associated with temozolomide. [2018]

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

Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms. [2023]

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

Safety and Feasibility of Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 Liver-Dominant Metastatic Neuroendocrine Tumors. [2019]