Chemotherapy for Pancreatic Cancer

Recruiting at 258 trial locations

Overseen By Jonathan R. Strosberg

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SWOG Cancer Research Network

Must not be taking: Warfarin

Disqualifiers: Metastatic disease, CNS 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: 10

Duration: 16 weeks

141 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of capecitabine and temozolomide after surgery in treating patients with high-risk well-differentiated pancreatic neuroendocrine tumors. 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. Giving capecitabine and temozolomide after surgery could prevent or delay the return of cancer in patients with high-risk well-differentiated pancreatic neuroendocrine tumors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take warfarin while on the trial. Other anticoagulants are allowed, and you should discuss your specific medications with the study team.

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

Research shows that capecitabine has been effective in treating advanced gastric and colorectal cancers, and temozolomide has shown activity in treating other types of tumors like melanoma and glioma. However, in a study specifically for pancreatic cancer, temozolomide alone was not effective, but the combination of capecitabine and temozolomide showed promise in treating pancreatic endocrine carcinomas. ^{1 2 3 4 5}

Is temozolomide generally safe for humans?

Temozolomide is generally well tolerated and safe, with common side effects like fatigue, nausea, and mild blood-related issues. However, it can sometimes cause serious blood problems, such as myelodysplastic syndrome (a bone marrow disorder) and aplastic anemia (a condition where the body stops producing enough new blood cells). ^{6 7 8 9 10}

How does the drug temozolomide differ from other treatments for pancreatic cancer?

Temozolomide is unique because it is an oral chemotherapy drug that is rapidly absorbed and has been used in other cancers like melanoma and glioma. However, it has shown limited effectiveness in treating pancreatic cancer, with most patients experiencing disease progression within two months. ^{2 3 11 12 13}

Research Team

Heloisa P Soares

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults who've had surgery for high-risk, well-differentiated pancreatic neuroendocrine tumors. They must be able to swallow pills, have no other active cancers (with some exceptions), and not have received certain treatments post-surgery. A complete medical history and physical exam are required, along with specific blood count and chemistry levels.

Inclusion Criteria

Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

I have had bleeding in my stomach or intestines.

Participants must have specific levels of blood cells and chemicals in their blood.

Exclusion Criteria

Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator

I do not have cancer spread to my brain or its coverings.

I have no allergies to medications similar to temozolomide or capecitabine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive capecitabine and temozolomide orally for up to 4 cycles, each cycle lasting 28 days

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months for 3 years, then annually

Treatment Details

Interventions

• Capecitabine
• Temozolomide

Trial Overview The trial tests the effectiveness of two chemotherapy drugs, capecitabine and temozolomide, given after surgery to prevent cancer from returning in patients with high-risk pancreatic neuroendocrine tumors. The study will observe how these drugs stop tumor cells from growing or spreading.

Participant Groups

Group I: Arm I (capecitabine, temozolomide) Experimental Treatment 2 Interventions

Patients receive capecitabine PO BID on days 1-14 and temozolomide PO once QD on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (surveillance) Active Control 1 Intervention

Patients undergo surveillance with no active treatment.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 42 patients with metastatic or locally advanced pancreatic cancer, capecitabine demonstrated a clinical benefit response in 24% of patients, improving pain intensity and overall performance status.

Capecitabine was generally well tolerated, with a 9.5% objective response rate, suggesting it may be a viable treatment option for further evaluation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. Cartwright, TH., Cohn, A., Varkey, JA., 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]

In a study involving 16 patients with advanced pancreatic adenocarcinoma, oral temozolomide at a dose of 200 mg/m2/day for 5 days showed no effective responses, with all 15 evaluable patients experiencing disease progression within 2 months.

While the treatment was associated with some hematological toxicity, including grade 3 neutropenia and thrombocytopenia in 3 patients, other side effects were relatively mild, indicating that temozolomide is not an effective option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of temozolomide in advanced untreated pancreatic cancer. Moore, MJ., Feld, R., Hedley, D., et al.[2022]

In a study of 61 patients with advanced pancreatic cancer who had previously undergone gemcitabine therapy, the combination of capecitabine and thalidomide showed a marginal improvement in progression-free survival (PFS) compared to capecitabine alone, with PFS of 3.1 months versus 2.8 months.

The combination treatment was generally well tolerated, with the most common side effect being grade 3 diarrhea, indicating that while the regimen is not highly effective, it can be safely administered to patients who have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of second-line treatment with capecitabine and thalidomide in patients with advanced pancreatic cancer]. Shi, SB., Ma, TH., Tang, XY., et al.[2018]

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]

A review of 5,127 reports on temozolomide (TMZ) revealed 112 cases of major hematologic adverse events (HAEs), with a significant number of these cases leading to death, highlighting the serious risks associated with this medication.

Aplastic anemia (AA) and leukemia were the most common major HAEs linked to TMZ, indicating a unique toxicity profile compared to other alkylating agents, and suggesting that patients should be informed about these risks, especially since AA can develop after a short duration of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic adverse events associated with temozolomide. Villano, JL., Letarte, N., Yu, JM., et al.[2018]

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]

The study confirmed that the generic temozolomide capsules (TOZ039) are bioequivalent to the brand Temodal® capsules, with pharmacokinetic parameters falling within the acceptable range for both 20-mg and 100-mg doses in 29 patients with brain tumors.

The treatment was found to be safe, with no treatment-related severe adverse events or mortality reported, although 82.8% of patients experienced some adverse effects, highlighting the importance of monitoring patient responses during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. Hu, C., Lin, Q., Liu, C., et al.[2021]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Combining temozolomide (TMZ) with O(6)-benzyl-guanine (BG) enhances the effectiveness of treatment in pancreatic tumors, particularly in cells with functional p53, as shown in studies using human and mouse cell lines.

The presence of p53 not only triggers apoptosis by delaying the cell cycle but also aids in cell death through the activation of mismatch repair mechanisms, indicating a complex role of p53 in the response to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of cell cycle checkpoints and p53 function on the toxicity of temozolomide in human pancreatic cancer cells. Gupta, S., Sathishkumar, S., Ahmed, MM.[2021]

The TMZ-resistant glioma cell line SF188/TR showed a 6-fold resistance to temozolomide and cross-resistance to various other anticancer agents, indicating a significant challenge in treating resistant tumors.

Increased activity of the enzyme alkylguanine alkyltransferase (AGT) was identified as a primary mechanism of resistance to TMZ, while changes in the balance of pro-apoptotic and anti-apoptotic proteins contributed to broader cross-resistance to other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Ma, J., Murphy, M., O'Dwyer, PJ., et al.[2022]

Fewer than 20% of pancreatic cancer patients have tumors confined to the pancreas, highlighting the need for effective treatment strategies for advanced disease, as about 40% present with locally advanced cancer.

Gemcitabine is established as the first-line treatment for pancreatic cancer, showing significant clinical benefits, and is being explored in combination with various other agents like 5-fluorouracil and irinotecan to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in the treatment of pancreatic cancer. Haller, DG.[2022]

References

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

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. [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

A phase II study of temozolomide in advanced untreated pancreatic cancer. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Effect of second-line treatment with capecitabine and thalidomide in patients with advanced pancreatic cancer]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Germany pubmed.ncbi.nlm.nih.gov

Hematologic adverse events associated with temozolomide. [2018]

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. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of cell cycle checkpoints and p53 function on the toxicity of temozolomide in human pancreatic cancer cells. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. [2022]

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

Future directions in the treatment of pancreatic cancer. [2022]