CapTem + Y90 for Neuroendocrine Cancer

(CapTemY90 Trial)

Recruiting at 2 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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2 evaluation of hepatic-progression free survival among patients with Grade 2 liver-dominant NET metastases undergoing combination therapy with CapTem and Y90 radioembolization.The hypothesis is to confirm safety and to assess if disease control is improved relative to expectation from either therapy alone.

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.

What data supports the effectiveness of the CapTem treatment for neuroendocrine cancer?

Research shows that the combination of capecitabine and temozolomide (CAPTEM) is effective in treating advanced neuroendocrine tumors, with high response rates reported in multiple studies. This suggests that the CapTem treatment could be beneficial for patients with neuroendocrine cancer. ^{1 2 3 4 5}

Is the CapTem + Y90 treatment generally safe for humans?

The combination of capecitabine and temozolomide (CapTem) has been studied for safety in patients with neuroendocrine tumors and other cancers, showing it is generally safe but may have risks like infections and blood-related side effects. More research is needed to fully understand rare toxicities and long-term effects. ^{1 2 5 6 7}

How is the CapTem + Y90 treatment different from other treatments for neuroendocrine cancer?

The CapTem + Y90 treatment is unique because it combines oral chemotherapy drugs, capecitabine and temozolomide, with Y90 radioembolization, a targeted radiation therapy, to treat neuroendocrine tumors, especially those that have spread to the liver. This combination leverages the radiosensitizing properties of the drugs to enhance the effectiveness of the radiation, potentially improving response rates and survival outcomes compared to standard treatments. ^{1 2 4 5 8}

Research Team

Michael Soulen, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

The optimal duration of capecitabine plus temozolomide in patients with well-differentiated pancreatic NETs with or without maintenance therapy. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. [2022]

7. United States 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. [2018]

8. 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]