Chemotherapy vs Radioactive Drug for Pancreatic Neuroendocrine Tumors

Recruiting at 180 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

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. 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 pancreatic neuroendocrine tumors.

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.

What data supports the effectiveness of the drug combination of Capecitabine, Xeloda, Lutetium Lu 177 Dotatate, Lutathera, and Temozolomide for treating pancreatic neuroendocrine tumors?

Research shows that combining Lutetium-177-dotatate with capecitabine and temozolomide is well tolerated and effective in controlling tumors in patients with advanced low-grade neuroendocrine tumors, with significant tumor response rates and prolonged survival. ^{1 2 3 4 5}

Is the combination of Lutetium Lu 177 Dotatate, Capecitabine, and Temozolomide safe for treating neuroendocrine tumors?

The combination of Lutetium Lu 177 Dotatate, Capecitabine, and Temozolomide was generally well tolerated in patients with advanced low-grade neuroendocrine tumors, with mild to moderate side effects such as nausea and low blood cell counts. ^{2 3 4 6 7}

How is the chemotherapy and radioactive drug treatment for pancreatic neuroendocrine tumors different from other treatments?

This treatment combines a radioactive drug, Lutetium Lu 177 Dotatate, with chemotherapy drugs Capecitabine and Temozolomide, which work together to target and kill cancer cells. This combination is unique because it uses both radiation and chemotherapy to enhance the treatment's effectiveness, showing promising results in controlling tumor growth in patients with advanced neuroendocrine tumors. ^{1 2 3 6 8}

Research Team

Timothy J. b, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. [2022]

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

First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. [2022]

3. United States 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. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies. [2020]

5. Poland 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. [2020]

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

Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: a Spanish multicenter experience. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours. [2021]

8. United States 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. [2021]