Chemotherapy for Neuroendocrine Cancer

Recruiting at 703 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: Coumadin, Antiretrovirals

Disqualifiers: Brain metastases, DPD deficiency, 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: 24

Duration: Up to 1 year

67 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications, but you cannot be on any investigational agents or Coumadin while participating. Other anticoagulants are allowed.

What data supports the effectiveness of the drug combination of capecitabine and temozolomide for neuroendocrine cancer?

Research shows that the combination of capecitabine and temozolomide is promising for treating well-differentiated neuroendocrine tumors, with manageable side effects and improved outcomes. In patients with metastatic pancreatic endocrine carcinomas, this combination has shown synergistic effects, enhancing the treatment's effectiveness. ^{1 2 3 4 5}

Is chemotherapy with temozolomide and capecitabine safe for treating neuroendocrine cancer?

Temozolomide and capecitabine have been used in treating neuroendocrine tumors, but significant treatment-related toxicity (side effects) has been reported. This means while they can be effective, they may also cause notable side effects in some patients. ^{1 3 5 6 7}

What makes the chemotherapy treatment for neuroendocrine cancer unique?

This treatment is unique because it combines capecitabine and temozolomide, which are taken orally, offering a more convenient option compared to traditional intravenous chemotherapy. This combination has shown promising results with manageable side effects, especially for well-differentiated neuroendocrine tumors, which are typically resistant to other chemotherapy options. ^{1 2 4 7 8}

What is the purpose of this trial?

This trial is testing two different sets of cancer drugs to see which works better for patients with advanced neuroendocrine carcinoma that has spread or cannot be removed by surgery. The drugs aim to stop cancer from growing and spreading by attacking the cancer cells in different ways. One of the drugs being tested is used for treating advanced neuroendocrine tumors.

Research Team

Jennifer Eads

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with advanced, inoperable or metastatic neuroendocrine carcinoma of the gastrointestinal tract or pancreas. They should not have had prior systemic treatment for this cancer and must be physically well enough to participate (ECOG 0-2). Participants need functioning major organs, no severe allergies to study drugs, no other cancers unless specific conditions are met, and cannot be pregnant. Effective contraception is advised.

Inclusion Criteria

The cells in your sample show rapid growth, or there are a lot of dividing cells in the sample.

My cancer's size can be measured and was checked by CT or MRI within the last 4 weeks.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I am allergic to certain chemotherapy drugs like cisplatin or carboplatin.

I do not have serious heart issues, unstable chest pain, irregular heartbeats, or major psychiatric/social situations that would prevent me from following the study's requirements.

I have no other cancers, except for certain allowed types.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either capecitabine and temozolomide or cisplatin/carboplatin and etoposide based on randomization

Up to 1 year

Courses repeat every 21-28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Capecitabine
• Carboplatin
• Cisplatin
• Etoposide
• Temozolomide

Trial Overview The trial compares two chemotherapy regimens: temozolomide plus capecitabine versus cisplatin or carboplatin with etoposide. It aims to determine which combination is more effective against certain types of neuroendocrine carcinomas that haven't responded well to standard treatments.

Participant Groups

Group I: Arm A (capecitabine, temozolomide) Experimental Treatment 3 Interventions

Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (cisplatin, carboplatin, etoposide) Active Control 4 Interventions

Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days 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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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 phase II trial involving 78 patients with advanced poorly differentiated neuroendocrine carcinomas, the chemotherapy regimen of paclitaxel, carboplatin, and etoposide resulted in a 53% major response rate, with 15% achieving complete responses and some remaining disease-free for up to 66 months.

The treatment demonstrated moderate toxicity, primarily myelosuppression, and showed no significant efficacy advantages over standard platinum/etoposide regimens, suggesting that similar treatment strategies used for small-cell lung cancer may be appropriate for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. Hainsworth, JD., Spigel, DR., Litchy, S., et al.[2015]

References

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

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors. [2020]

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

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

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

Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. [2022]

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

Temozolomide alone or in combination with capecitabine in patients with advanced neuroendocrine neoplasms: an Italian multicenter real-world analysis. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Activity of Metronomic Temozolomide in Second-Line Treatment of Advanced Neuroendocrine Neoplasms. [2020]

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

Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors. [2019]

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

Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. [2015]