What side effects are associated with this type of intervention?

The combination of Capecitabine and Temozolomide, both of which are chemotherapeutic agents, is commonly used in the treatment of neuroendocrine tumors. Known side effects of Capecitabine include hand-foot syndrome, diarrhea, nausea, and fatigue. Temozolomide can cause myelosuppression, leading to anemia, leukopenia, and thrombocytopenia, as well as nausea and vomiting. Yttrium-90 Radioembolization, a form of targeted radiation therapy, can result in liver toxicity, fatigue, abdominal pain, and, in some cases, radiation-induced liver disease. Combining these treatments can lead to additive toxicities, but studies have shown that the combination is generally well-tolerated with manageable side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Neuroendocrine Tumors (NETs) that involve radiosensitization and targeted radiation therapy. One notable approval is for Lutetium Lu 177 dotatate (Lutathera), a radiolabeled somatostatin analog used in Peptide Receptor Radionuclide Therapy (PRRT) for gastroenteropancreatic NETs. This treatment targets somatostatin receptors on tumor cells, delivering targeted radiation. Additionally, Everolimus (Afinitor) has been approved for advanced NETs, working as an mTOR inhibitor to slow tumor growth. While Capecitabine and Temozolomide are not specifically approved for NETs, they are used off-label in combination therapies due to their radiosensitizing properties, enhancing the efficacy of treatments like Yttrium-90 radioembolization.

What other types of research exist?

Promising alternatives to Capecitabine and Temozolomide with Yttrium-90 Radioembolization for NETs include Peptide Receptor Radionuclide Therapy (PRRT) with Lutetium-177 dotatate, which has shown efficacy in treating somatostatin-receptor positive NETs. Additionally, targeted alpha-particle therapy with Actinium-225 DOTATATE and Bismuth-213 DOTATATE are emerging options that have demonstrated potential in early studies. These therapies offer targeted radiation with radiosensitizing properties and may provide effective treatment alternatives for NET patients.

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Anti-metabolites

CapTem + Radioembolization for Liver Metastases from Neuroendocrine Tumors (CapTemY90 Trial)

Phase 2

Recruiting

Led By MICHAEL C SOULEN, MD

Research Sponsored by Abramson Cancer Center of the University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with confirmed diagnosis of histologic grade 2 neuroendocrine tumor with unresectable liver metastases (primary tumor or other extrahepatic disease may be present)

Patent main portal vein

Must not have

Contraindications to capecitabine or temozolomide

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include those related to chemotherapy like nausea, fatigue, low blood counts leading to increased infection risk or bleeding problems; as well as specific risks from radioembolization such as abdominal pain or potential damage to non-target organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My main portal vein is open and not blocked.

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I have a liver tumor larger than 1cm that can be measured.

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My liver cancer affects less than half of my liver.

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I am older than 18 years.

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Half or more of my cancer is in my liver.

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My liver is functioning well, based on recent tests.

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My blood platelets, kidney function, and blood clotting levels are within the required range.

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I can take care of myself and perform daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot take capecitabine or temozolomide due to health reasons.

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I do not have any uncontrolled illnesses like heart problems or infections.

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I have had surgery or a procedure to open my bile duct.

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I am not eligible for a specific liver cancer treatment due to high risk of complications.

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I cannot have iodine-based contrast due to a severe past reaction.

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I have had treatment directly to my liver using embolization or Y-90.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

intra-hepatic progression-free survival

Secondary study objectives

Chromogrannin A level

EORTC QLQ-GINET21

Intra-hepatic and extra-hepatic tumor responses

+2 more

Trial Design

1Treatment groups

Experimental Treatment

Group I: CapTemY90Experimental Treatment1 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.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Capecitabine and temozolomide are chemotherapeutic agents that act as radiosensitizers, enhancing the effectiveness of radiation therapy. Capecitabine is a prodrug that converts to 5-fluorouracil (5-FU) in the body, inhibiting DNA synthesis and cell division. Temozolomide is an alkylating agent that damages DNA, leading to cell death. Yttrium-90 radioembolization involves injecting radioactive microspheres into the liver's blood supply, delivering targeted radiation to liver metastases. This combination leverages the DNA-damaging effects of chemotherapy with localized radiation, potentially improving tumor control and patient outcomes. For NET patients, this integrated approach may offer better disease management by maximizing tumor cell kill while minimizing systemic toxicity.

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