CapTem + Radioembolization for Liver Metastases from Neuroendocrine Tumors

(CapTemY90 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Michael Soulen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

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.

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.

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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.

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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.

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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

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Abramson Cancer Center Philadelphia, PA

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania Lead Sponsor

Roswell Park Cancer Institute Collaborator

CARTI Collaborator

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] We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).

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

Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms. [2020] Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers.

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

Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. [2023] Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs).

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

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group. [2023] This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs).

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] Capecitabine-Temozolomide (CapTem) is an oral chemotherapy regimen for NETs. Both drugs are radiosensitizers. Integrating CapTem and Y90 transarterial radioembolization (TARE) in patients with grade 2 neuroendocrine tumor (NET) liver metastases achieved an encouraging objective response rate (ORR) and progression-free survival (PFS) in a feasibility study. This study expands that report to a larger cohort with longer follow-up.

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

Hematologic adverse events associated with temozolomide. [2018] Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available.

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

Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms. [2023] The capecitabine/temozolomide (CAPTEM) regimen has significant activity in advanced neuroendocrine tumors (NETs). Questions exist regarding activity in pancreatic versus nonpancreatic NETs, risk of opportunistic infections, long-term myelotoxicity, and safety of prolonged treatment duration. Analysis of large patient cohorts is needed for the evaluation of rare toxicities and assessment of risk factors.

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] An integrated protocol combining capecitibine-temozolomide with yttrium-90 radioembolization (CapTemY90) for liver-dominant grade 2 neuroendocrine tumors (NETs) was designed in the hope of achieving synergistic improvement in liver disease control with no more than additive toxicities. This report describes the feasibility and safety of this regimen.