Chemotherapy for Pancreatic Cancer

Recruiting at 261 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two chemotherapy drugs, capecitabine (Xeloda) and temozolomide (Temodar), can prevent the return of pancreatic neuroendocrine tumors after surgery. The researchers aim to determine if these drugs can prevent or delay cancer recurrence by killing or stopping the growth of cancer cells. Participants will either receive these drugs or undergo monitoring without active treatment. This trial targets individuals who have had a specific type of pancreatic tumor removed and show no signs of cancer spreading. Eligible participants should have recently undergone surgical tumor removal and must not have any other known active cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that patients generally tolerate the combination of capecitabine and temozolomide well. Studies have found that these drugs can help slow cancer growth. Regarding safety, about 93.8% of people experienced mild side effects, while around 23.7% faced more serious ones. These findings suggest the treatment is fairly safe, though some risks are involved, as with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of capecitabine and temozolomide for pancreatic cancer because it offers a fresh approach compared to the standard treatments like gemcitabine and FOLFIRINOX. Capecitabine and temozolomide work together by attacking cancer cells in different ways, potentially enhancing the overall effectiveness of the treatment. This combination is administered orally, which can be more convenient and less invasive than the intravenous methods typically used in standard therapies. Additionally, this regimen is designed to be administered in cycles, which might help in managing side effects more effectively while maintaining its potency against the cancer.

What evidence suggests that capecitabine and temozolomide might be effective for pancreatic cancer?

Research has shown that using capecitabine and temozolomide together can effectively treat certain cancers. In this trial, participants in one arm will receive this combination. One study demonstrated that this combination helped patients live longer without their cancer worsening, compared to using temozolomide alone. Another study found that patients had an average of 16.1 months before their cancer progressed, and 92% were still alive after two years. These results suggest the treatment might help delay the return or spread of cancer. Additionally, only a few patients experienced severe side effects. These findings indicate that capecitabine and temozolomide could be promising for patients with high-risk pancreatic neuroendocrine tumors. ^{2 4 6 7 8}

Who Is on the Research Team?

Heloisa P Soares

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

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]

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]

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]

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]

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]

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]

Citations

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

Outcomes of capecitabine plus temozolomide combination ... The median progression-free survival was 5.3 months (95% confidence interval [CI]: 0.9-NA), and 1-year survival rate was 81.2% (95% CI: 41.5-95.2%).

2. 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 ...

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

Efficacy of Capecitabine and Temozolomide Regimen in ... First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and ...

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

First-Line Chemotherapy With Capecitabine and ... The rate of survival at two years was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events. CONCLUSIONS. The combination of capecitabine and ...

5. 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 ...

6. 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.

7. 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): 759 ...

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11926-2

Efficacy and safety of temozolomide-based regimens in ... Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% ...