CapTem + Y90 for Neuroendocrine Cancer

(CapTemY90 Trial)

Recruiting at 3 trial locations

Overseen By Veronica Faris

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: Investigational agents

Disqualifiers: Previous embolization, Uncontrolled illness, Pregnancy, 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 progression or intolerance

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with neuroendocrine cancer that has spread to the liver. It aims to determine if using CapTem (a mix of two oral medications, Capecitabine and Temozolomide) with Y90 radioembolization (a type of targeted radiation therapy) can better control the cancer compared to each treatment alone. The trial seeks participants with Grade 2 or 3 well-differentiated neuroendocrine tumors that cannot be surgically removed and primarily affect the liver. Participants should have active liver tumors comprising less than half of their liver and should not have previously tried similar treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

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

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

Research has shown that combining Capecitabine and Temozolomide (CapTem) with Y90 radioembolization is generally safe. Studies have found that patients with advanced neuroendocrine tumors usually tolerate this treatment well, with most not experiencing severe side effects.

In one study, patients who received CapTem and Y90 radioembolization maintained good control over their liver tumors for an extended period, with no major safety issues. Another study confirmed that radioembolization for liver tumors was both effective and safe.

Overall, while some side effects can occur, research indicates that the treatment has been safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the CapTem + Y90 treatment for neuroendocrine cancer because it combines chemotherapy with a targeted radioembolization approach. While traditional treatments might rely solely on chemotherapy or external radiation, this approach uses capecitabine and temozolomide to weaken cancer cells, followed by Y90 radioembolization to deliver radiation directly into the tumor. This targeted delivery could potentially enhance effectiveness and reduce side effects compared to conventional therapies. By integrating these methods, the treatment might offer a more comprehensive attack on cancer cells, offering hope for improved outcomes in patients.

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

Research has shown that combining capecitabine and temozolomide (CapTem) can effectively treat neuroendocrine tumors (NETs). Studies have found that this combination improves outcomes such as tumor response, progression-free survival, and overall survival rates. In this trial, participants will receive CapTem alongside Y90 radioembolization. Previous studies suggest that using CapTem with Y90 radioembolization effectively controls Grade 2 NETs that have spread to the liver. This indicates that adding Y90 radioembolization could better manage liver tumors. Early results from these studies suggest that this combined therapy might be more effective than using either treatment alone. ^{3 4 5 6 7}

Who Is on the Research Team?

Michael Soulen, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults over 18 with Grade 2 neuroendocrine tumors and liver metastases that can't be removed by surgery. They should have a life expectancy of more than 6 months, stable health, and not have had chemotherapy or radiotherapy in the last 4 weeks. Liver function must be within certain limits, and they need to use effective contraception if capable of childbearing.

Inclusion Criteria

Less than half of my liver is affected by cancer.

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

My liver is working well, based on recent tests.

Exclusion Criteria

Contraindicated for both contrast-enhanced MRI and CT

I cannot take capecitabine or temozolomide due to adverse reactions.

I cannot have a specific liver cancer treatment due to high risk of complications.

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) and undergo Yttrium-90 radioembolization. Capecitabine is administered 750 mg/m2 twice daily orally for 14 days and Temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles. TARE is performed on Day 7 of Cycle 2 and, if needed, on Day 7 of Cycle 3 or 4.

Until progression or intolerance

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including tumor markers and quality of life evaluations every 3 months for 24 months.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine Oral Product
• Temozolomide Oral Product
• transarterial radioembolization

Trial Overview The trial is testing how well patients with specific liver tumors respond to a combination therapy using Capecitabine, Temozolomide (oral medications), and Y90 radioembolization compared to previous treatments. It's a Phase 2 study focusing on whether this mix can safely improve disease control.

How Is the Trial Designed?

Group I: Oral CapTem + Y90 Radioembolization Experimental Treatment 3 Interventions

Capecitabine 750 mg/m2 twice daily orally for 14 days and temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles, to be continued until 1) disease progression or 2) intolerable toxicities. Trans-arterial radioembolization (TARE) on Day 7 of cycle 2 and, if needed for the other lobe, Day 7 of either cycle 3 or 4.

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

Approved in European Union as Xeloda for:

• Breast cancer
• Gastric cancer
• Colorectal cancer

Approved in United States as Xeloda for:

• Metastatic colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Metastatic colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

University of Miami Sylvester Comprehensive Cancer Center

Collaborator

Trials

11

Recruited

2,700+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

CARTI

Collaborator

Trials

3

Recruited

610+

Published Research Related to This Trial

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]

In a study of 44 previously untreated patients with advanced gastric cancer, capecitabine demonstrated an objective response rate of 34% and a median overall survival of 9.5 months, indicating its efficacy as a first-line treatment.

Capecitabine was generally well tolerated, with the most common side effects being hand-foot syndrome and nausea, and severe myelosuppression was not observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Hong, YS., Song, SY., Lee, SI., et al.[2022]

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]

In a Phase I clinical trial involving 24 patients with brain metastases from breast cancer, the combination of temozolomide and capecitabine demonstrated significant antitumor activity, achieving an 18% objective response rate with 1 complete and 3 partial responses.

The treatment was well-tolerated, with fatigue and nausea being the most common side effects, and it showed potential for maintaining or improving neurocognitive function in patients with stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Rivera, E., Meyers, C., Groves, M., et al.[2018]

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 94 patients with metastatic pancreatic neuroendocrine tumors (PanNETs), prolonged treatment with capecitabine and temozolomide (CapTem) showed significantly higher objective response rates (73.3% and 41.9% for prolonged therapy) compared to fixed cycles (20%).

Patients receiving prolonged CapTem and maintenance therapy had a median progression-free survival of 35 months and 26 months, respectively, which was significantly better than the 19 months observed in those who received fixed cycles, indicating that extended treatment may enhance outcomes with manageable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The optimal duration of capecitabine plus temozolomide in patients with well-differentiated pancreatic NETs with or without maintenance therapy. Gao, H., Dong, J., Zhang, W., et al.[2022]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5732786/

Combination therapy with capecitabine and temozolomide ... Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology.

2. academic.oup.com academic.oup.com/oncolo/article/28/10/875/7263101

Efficacy of Capecitabine and Temozolomide Regimen in ... We found that first-line CAPTEM treatment yielded higher ORR, PFS, and OS benefits compared to other lines of treatment regardless of tumor ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38057498/

Long-Term Outcomes of a Single-Institution Retrospective Study Conclusion: Chemoradiation with CapTem and TARE provided durable control of G2 NET liver metastases for substantially longer than expectations ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-00831

Capecitabine and Temozolomide with A Specific Form of ... Giving capecitabine and temozolomide with transarterial radioembolization may help improve tumor control in the liver. Eligibility Criteria ...

5. researchgate.net researchgate.net/publication/320605880_Combination_therapy_with_capecitabine_and_temozolomide_in_patients_with_low_and_high_grade_neuroendocrine_tumors_with_an_exploratory_analysis_of_O6-methylguanine_DNA_methyltransferase_as_a_biomarker_f

Combination therapy with capecitabine and temozolomide ... Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12131736/

Radioembolization for neuroendocrine tumors: procedure, ... The purpose of this review is to evaluate the current role of selective internal radiation therapy (radioembolization) as a treatment for ...

7. ageb.be ageb.be/Articles/Volume%2088%20(2025)/Fasc1/02-Briol-et-al.pdf

Selective internal radiation therapy for neuroendocrine liver ... Background and study aims: Selective internal radiation therapy. (SIRT) has shown good results in unresectable liver metastases from neuroendocrine ...