Chemotherapy vs Radioactive Drug for Pancreatic Neuroendocrine Tumors

Not currently recruiting at 185 trial locations

Overseen By Timothy J. Hobday, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Somatostatin analogs

Must not be taking: Temozolomide, Capecitabine, PRRT

Disqualifiers: Poorly differentiated carcinoma, brain metastases, 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: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to determine which is more effective for advanced pancreatic neuroendocrine tumors that cannot be surgically removed. One treatment uses chemotherapy drugs, capecitabine (Xeloda) and temozolomide, which target and stop tumor cell growth. The other treatment uses a radioactive drug, lutetium Lu 177 dotatate (Lutathera), to deliver radiation directly to tumor cells, potentially minimizing damage to normal cells. The trial seeks participants with pancreatic neuroendocrine tumors that have spread beyond the pancreas, especially those experiencing symptoms like pain, difficulty eating, or hormone-related issues that are difficult to manage. As a Phase 2 trial, the 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, it allows the use of somatostatin analogs under certain conditions, so you might be able to continue some treatments. It's best to discuss your specific medications with the trial team.

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

Research has shown that lutetium Lu 177 dotatate is generally safe for people with neuroendocrine tumors. In studies involving 360 patients, the treatment demonstrated an acceptable safety profile, with most participants not experiencing severe side effects. Another study confirmed its safety, noting no harm to important organs.

For the combination of capecitabine and temozolomide, research indicates it is well-tolerated, with many patients not experiencing serious issues. It is also approved for other conditions, suggesting safety in various situations.

Both treatments have been shown to be safe options, but individual reactions can vary. Always consult a healthcare provider to understand what this might mean for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new approaches to tackling pancreatic neuroendocrine tumors. Unlike traditional chemotherapy, which broadly targets fast-growing cells, Lutetium Lu 177 Dotatate uses targeted radiotherapy, delivering radiation directly to the tumor cells. This precision can potentially reduce side effects and improve effectiveness. On the other hand, the combination of capecitabine and temozolomide offers a dual-action approach by disrupting the DNA of cancer cells, potentially enhancing tumor control with oral medications that are more convenient for patients. These innovative strategies could provide new hope for those battling this challenging condition.

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

Research shows that lutetium Lu 177 dotatate, which participants in this trial may receive, effectively treats advanced neuroendocrine tumors. Studies found it can significantly delay cancer progression, with patients living almost three times longer without their cancer worsening compared to other treatments. The treatment also achieved a 43% overall response rate, which is promising. Meanwhile, the combination of capecitabine and temozolomide, another treatment option in this trial, has successfully extended the time pancreatic neuroendocrine tumors do not worsen. Specifically, patients treated with this combination had a median time of up to 15.9 months before their cancer progressed, which is a positive outcome. Both treatment options in this trial show potential in effectively managing this type of cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Timothy J. b, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults with advanced pancreatic neuroendocrine tumors (well-differentiated G1, G2, or well-differentiated G3) that can't be surgically removed and have spread. Eligible participants may have symptoms from the tumor or hormone excess not controlled by medication, must show tumor growth on scans within the past year, and could have had certain previous treatments but not specific chemotherapy drugs or peptide receptor radionuclide therapy (PRRT).

Inclusion Criteria

I have previously been treated with specific cancer drugs like mTOR or VEGF inhibitors.

Your albumin level in the blood is at least 3.0 grams per deciliter.

I've been on a stable dose of somatostatin analog for 3+ months for my functional tumor and it has grown despite the treatment.

Exclusion Criteria

I can swallow normally and my stomach and intestines absorb medications as they should.

My brain metastases are treated, stable, and I've been off treatment for 2 months.

My heart condition is stable and not severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Arm I: Lutetium Lu 177 Dotatate)

Participants receive lutetium Lu 177 dotatate IV over 30 minutes on day 1. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

32 weeks

4 visits (in-person)

Treatment (Arm II: Capecitabine and Temozolomide)

Participants receive capecitabine orally twice daily on days 1-14 and temozolomide orally once daily on days 10-14. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Lutetium Lu 177 Dotatate
• Temozolomide

Trial Overview The trial is testing whether a combination of chemotherapy drugs Capecitabine and Temozolomide is more effective than Lutetium Lu 177 Dotatate, a radioactive drug targeting cancer cells while sparing normal ones. Participants will also complete questionnaires to assess their quality of life during treatment.

How Is the Trial Designed?

Group I: Arm II (capecitabin, temozolomide) Experimental Treatment 3 Interventions

Patients receive capecitabine PO BID days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (lutetium Lu 177 dotatate) Experimental Treatment 3 Interventions

Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

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?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 33 patients with advanced pulmonary carcinoids treated with CAPTEM chemotherapy, 18% achieved a partial response and 58% had stable disease, indicating modest efficacy in this patient population.

The median progression-free survival was 9.0 months and overall survival was 30.4 months, suggesting that while CAPTEM can provide some benefit, its effectiveness may vary, especially in patients with multi-organ metastasis when treated later in their treatment course.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours. Papaxoinis, G., Kordatou, Z., McCallum, L., et al.[2021]

In a study of 65 patients with grade 1/2 neuroendocrine tumors, capecitabine and temozolomide chemotherapy resulted in a response rate of 47.7%, with a median progression-free survival of 16.1 months and overall survival of 38.3 months.

The treatment was generally well-tolerated, with only 13.8% of patients experiencing severe toxicities, indicating that this chemotherapy combination is a promising option for managing both pancreatic and non-pancreatic neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: a Spanish multicenter experience. Crespo, G., Jiménez-Fonseca, P., Custodio, A., et al.[2018]

Lutetium-177-dotatate (177 Lu-dotatate) is an FDA-approved treatment for advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), based on positive results from the NETTER-1 trial.

A case study presented shows that a patient with a grade 3 pancreatic neuroendocrine tumor and a BRCA1 germline mutation experienced a significant response to 177 Lu-dotatate, suggesting its potential efficacy even in more aggressive tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. Zhu, M., Bassam Sonbol, M., Halfdanarson, T., et al.[2022]

The combination of lutetium-177 (177Lu)-octreotate with capecitabine and temozolomide was well tolerated in a phase I-II trial involving 35 patients with advanced low-grade neuroendocrine tumors, with no severe toxicities observed and only mild to moderate adverse effects reported.

The treatment demonstrated significant efficacy, achieving a complete response in 15% and a partial response in 38% of patients, with a median progression-free survival of 31 months, indicating strong tumor control rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Claringbold, PG., Price, RA., Turner, JH.[2022]

In a study of 76 patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), the combination of 177Lu-DOTATATE and capecitabine showed a significantly higher objective response rate (38%) and longer progression-free survival (54 months) compared to octreotide LAR, which had a 15% response rate and 16 months of progression-free survival.

Both treatment regimens had similar rates of severe side effects (grade 3 or 4 toxicities), indicating that while 177Lu-DOTATATE plus capecitabine is more effective, it does not appear to increase the risk of serious adverse events compared to octreotide LAR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience. Satapathy, S., Mittal, BR., Sood, A., et al.[2021]

In a study of 30 patients with metastatic pancreatic endocrine carcinomas, the combination of capecitabine and temozolomide resulted in a remarkable 70% objective response rate and a median progression-free survival of 18 months.

The treatment showed a high two-year survival rate of 92% with only 12% of patients experiencing severe adverse events, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Strosberg, JR., Fine, RL., Choi, J., et al.[2022]

In a retrospective study of 32 patients, the combination of capecitabine and temozolomide showed a significantly higher disease control rate in patients with grade 3 neuroendocrine tumors (70%) compared to those with neuroendocrine carcinomas (30%).

Patients with grade 3 neuroendocrine tumors experienced a median progression-free survival of 15.3 months and a median overall survival of 22 months, indicating that this treatment is effective for this specific group, while outcomes for neuroendocrine carcinomas were much poorer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma - retrospective analysis. Rogowski, W., Wachuła, E., Gorzelak, A., et al.[2020]

The combination of temozolomide (TMZ) followed by lutetium-177-labelled octreotate ((177)Lu-TATE) treatment significantly enhances therapeutic effects in neuroendocrine tumors, with 90% of mice showing complete tumor response when (177)Lu-TATE was administered 14 days after TMZ.

Molecular imaging techniques revealed that TMZ treatment increased the uptake of the somatostatin analogue (111)In-octreotide, suggesting that administering TMZ before (177)Lu-TATE optimizes the delivery of radioactivity to tumors, potentially improving outcomes for patients with SSTR-overexpressing neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies. Bison, SM., Haeck, JC., Bol, K., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40346312/

Outcomes of capecitabine plus temozolomide combination ... The objective response rates and disease control rates were 26.7 and 66.7%, respectively. The median observation period was 20.8 months. The median progression- ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e23064

Outcomes of temozolomide and capecitabine ... Capecitabine and temozolomide (CAPTEM) have proven effective in improving progression-free survival (PFS) in pancreatic neuroendocrine tumors (PNETs).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110496/

Outcomes of patients treated with capecitabine and ... Patients with PNETs who received CapTem in the first-line setting had a median PFS of 15.9 months as compared to only 3.1 months for the remainder [P=0.047, ...

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

Efficacy of Capecitabine and Temozolomide Regimen in ... Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT88857

Memorial Sloan-Kettering Cancer Center experience. The efficacy of capecitabine and temozolomide for the treatment of metastatic neuroendocrine tumors: Memorial Sloan-Kettering Cancer Center experience.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4665634/

First-Line Chemotherapy With Capecitabine and ... In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05247905

Study Details | NCT05247905 | Comparing Capecitabine ... The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01013

Randomized Study of Temozolomide or ... The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11603466/

Efficacy, safety, and prognostic factors of capecitabine plus ... CapTem is an effective and well-tolerated treatment for ATC patients. Pretreatment PLR and age appear to be potential prognostic markers for CapTem therapy.

10. ageb.be ageb.be/Articles/Volume%2088%20(2025)/Fasc2/6-Lambrechts%20et%20al.pdf

Efficacy and safety of capecitabine-temozolomide (CAPTEM ... Analysis of potential response predictors to capecitabine/ temozolomide in metastatic pancreatic neuroendocrine tumors. Endocr. Relat. Cancer., 2016, 23(9): ...