Glufosfamide vs Fluorouracil for Pancreatic Cancer

Recruiting at19 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Eleison Pharmaceuticals LLC.

Must not be taking: Antibiotics, Insulin

Disqualifiers: Diabetes, Brain metastases, Cardiovascular, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if the chemotherapy drug glufosfamide can help people with advanced pancreatic cancer live longer. These patients have already tried another treatment called gemcitabine, which didn't work for them. Glufosfamide aims to stop cancer cells from growing by damaging their DNA.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had any hormonal therapy, radiation therapy, biologic therapy, chemotherapy, or other systemic antitumor therapy for pancreatic cancer within 14 days before starting the trial.

What data supports the effectiveness of the drug 5-Fluorouracil (5-FU) for pancreatic cancer?

5-Fluorouracil (5-FU) is often used in combination with other drugs for treating pancreatic cancer, but its effectiveness is generally limited. In some studies, it showed partial responses in a small percentage of patients, and when combined with other drugs like leucovorin, it slightly improved survival rates. ^{1 2 3 4 5}

Is 5-Fluorouracil (5-FU) generally safe for humans?

5-Fluorouracil (5-FU) has been studied in various trials and is known to cause side effects like nausea, vomiting, and stomatitis (mouth sores), with some cases requiring hospitalization. While these side effects can be significant, they are generally reversible. ^{6 7 8 9 10}

What makes the drug Glufosfamide unique for treating pancreatic cancer?

Glufosfamide is unique because it combines the chemotherapy drug 5-fluorouracil (5-FU) with a glucose molecule, potentially enhancing its delivery to cancer cells, which often consume more glucose than normal cells. This targeted approach aims to improve the effectiveness of 5-FU in treating pancreatic cancer, which is typically resistant to conventional chemotherapy. ^{1 2 11 12 13}

Research Team

Edwin Thomas

Principal Investigator

Eleison Pharmaceuticals

Eligibility Criteria

This trial is for adults with metastatic pancreatic cancer who have not responded to gemcitabine-based treatment. They must be in good physical condition, able to consent, and agree to use contraception. Exclusions include symptomatic brain metastases, active infections or other cancers, recent major surgery without recovery, significant lab abnormalities, pregnancy or breastfeeding, insulin-dependent diabetes, and certain heart conditions.

Inclusion Criteria

Measurable or nonmeasurable disease by RECIST criteria (at least one target or nontarget lesion)

I agree to use effective contraception during and for 6 months after the study.

My pancreatic cancer was confirmed through a biopsy.

Exclusion Criteria

I haven't had any cancer treatments for my pancreatic cancer in the last 14 days.

I had major surgery less than 3 weeks ago and haven't fully recovered.

I am currently taking antibiotics for a serious infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either glufosfamide or 5-FU. Glufosfamide is administered as 4500 mg/m2 IV over 6 hours on Day 1 of each 21-day cycle. 5-FU is administered as 600 mg/m2 IV over 30 minutes on Day 1 of each week.

3-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fluorouracil (Anti-metabolites)
• Glufosfamide (Alkylating agents)

Trial Overview The study compares the effectiveness of glufosfamide versus fluorouracil (5-FU) in improving survival for patients with advanced pancreatic cancer after first-line therapy failure. Participants will receive either glufosfamide or bolus 5-FU as a second-line treatment option.

Participant Groups

Group I: glufosfamide Experimental Treatment 1 Intervention

Glufosfamide: 4500 mg/m2 IV over 6 hours on Day 1 of each 21-day cycle

Group II: 5-FU Active Control 1 Intervention

Fluorouracil (5-FU): 600 mg/m2 IV over 30 minutes on Day 1 of each week

Fluorouracil is already approved in Canada for the following indications:

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Eleison Pharmaceuticals LLC.

Lead Sponsor

Trials

4

Recruited

550+

Findings from Research

The study developed a method to deliver 5-fluorouracil (5FU) specifically to pancreatic cancer cells using epidermal growth factor receptor (EGFR)-targeted aptamers, which showed effective tumor reduction in various models, including patient-derived organoids and genetically engineered mice.

This targeted delivery approach not only enhanced the efficacy of 5FU in both sensitive and resistant pancreatic cancer cell lines but also demonstrated the potential to improve treatment outcomes for patients with pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-Specific Delivery of 5-Fluorouracil-Incorporated Epidermal Growth Factor Receptor-Targeted Aptamers as an Efficient Treatment in Pancreatic Ductal Adenocarcinoma Models. Mahajan, UM., Li, Q., Alnatsha, A., et al.[2022]

In a study of 74 patients with advanced pancreatic cancer, gemcitabine was found to be the most effective chemotherapy regimen, with an average survival of 7.9 months, compared to 4.4 months for FAM, 4.2 months for 5FU, and 5.6 months for 5FU plus leukovorin.

Overall, chemotherapy provided a modest increase in survival (20%) for patients, with partial responses observed in 30% of those treated with gemcitabine, indicating its potential as a palliative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience with chemotherapy for advanced pancreatic carcinoma]. Kokhanenko, NIu., Gershanovich, ML., Ignashov, AM., et al.[2022]

In a study involving 16 patients with advanced pancreatic adenocarcinoma, continuous infusion of ifosfamide and 5-fluorouracil (5-FU) resulted in a low response rate of only 7%, indicating limited efficacy of this treatment approach.

While the continuous infusion method was feasible for outpatient treatment and showed a potentially better toxicity profile for ifosfamide, it did not demonstrate improved effectiveness compared to traditional bolus or short-term infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients with advanced adenocarcinoma of the pancreas. Poorter, RL., Bakker, PJ., Huizing, MT., et al.[2020]

In a study of 18 patients with advanced pancreatic cancer, continuous venous infusion of 5-fluorouracil (5FU) showed some efficacy, with 3 out of 10 patients experiencing a significant decrease in serum CA19-9 levels after treatment, indicating a potential response to therapy.

Despite the treatment, 10 patients had no change in their condition, and 4 experienced disease progression, suggesting that while 5FU may help some patients, it does not work for everyone and highlights the need for further research into effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer. Tajiri, H., Yoshimori, M., Okazaki, N., et al.[2018]

In a phase II study involving 19 patients with unresectable pancreatic adenocarcinomas, the combination of cisplatin, 5-fluorouracil, and leucovorin resulted in a modest response rate, with one complete response and two partial responses (15.8%).

Although the treatment was associated with reversible and tolerable adverse effects, the overall limited efficacy means it cannot be recommended as a standard therapy for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, 5-Fluorouracil, and leucovorin in the therapy of adenocarcinomas of the pancreas. Jones, D., Sugarman, S., Markowitz, A., et al.[2019]

The new 5-fluorouracil derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU), shows promising efficacy against various tumors in experimental models, outperforming both 5-FU and FT-207.

In a phase I study involving major institutions in Japan, HCFU demonstrated a dose-dependent incidence of side effects, primarily causing hot sensations and increased urination, but did not lead to significant changes in blood or serum biochemistry, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of a new antimetabolic agent 1-hexylcarbamoyl-5-fluorouracil (HCFU). Taguchi, T.[2021]

In a multi-institutional randomized trial involving patients with non-resectable pancreatic or biliary tract cancer, the modified FAM therapy (5-FU, ADR, MMC) did not show a significant improvement in overall survival or clinical effect compared to 5-FU mono-therapy.

While both treatment groups experienced similar primary adverse effects, the FAM group had a higher incidence of hair loss, and there was a tendency for improved survival duration in the FAM group specifically for gallbladder cancer, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]. Takada, T., Kato, H., Sasaki, M., et al.[2013]

In a phase II study involving 90 patients with advanced pancreatic cancer, the combination of 5-fluorouracil, folinic acid, and gemcitabine resulted in a 1-year survival rate of 25% and a median overall survival of 6.8 months, indicating its potential efficacy.

The treatment was well tolerated, with serious adverse events occurring in only 10% of patients, suggesting that this regimen has a low frequency of toxicities and is suitable for patients who cannot take oral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment of pancreatic cancer patients with the combination of 5-fluorouracil/folinic acid plus gemcitabine: a multicenter phase II trial by the CONKO-study group. Pelzer, U., Arnold, D., Reitzig, P., et al.[2022]

In a phase II study involving 23 patients with metastatic pancreatic carcinoma, the combination of 5-fluorouracil, leucovorin, and interferon alpha-2a showed no objective clinical responses, with 14 out of 18 evaluable patients experiencing disease progression.

The treatment was associated with significant toxicity, primarily nausea and vomiting, leading to notable hospitalization rates, indicating that this regimen is ineffective and poses considerable risks even for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial. David, AK., Vaughn, DJ., Holroyde, CP., et al.[2019]

In a phase I study involving 13 patients with intra-abdominal cancers, a continuous infusion of fluorouracil (5-FU) combined with high-dose folinic acid was found to be feasible, with a recommended dose of 500 mg/m2/day due to manageable side effects.

The study confirmed a significant pharmacokinetic advantage of intraperitoneal 5-FU, showing a much higher concentration in the abdominal cavity compared to the bloodstream, which could enhance its effectiveness in treating colorectal cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Continuous double administration of 5 fluorouracil (intravenous and intraperitoneal) modulated by folinic acid: phase I clinical study and pharmacokinetics in patients with intra-abdominal developing cancers]. de Forni, M., Gualano, V., Canal, P., et al.[2013]

Pancreatic adenocarcinoma is highly resistant to conventional chemotherapy, with 5-fluorouracil (5-FU) showing a declining response rate from 28% in the 1980s to 5-15% in recent studies, indicating a need for more effective treatments.

Gemcitabine has emerged as a promising alternative, demonstrating a response rate of 10-15% and significant improvements in performance status and clinical symptoms compared to 5-FU, with a median survival advantage of 5.6 months versus 4.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Possibilities of palliation in pancreatic cancer]. Di Costanzo, F., Sdrobolini, A., Gasperoni, S.[2017]

In a study of 54 patients with advanced pancreatic cancer, the combination of protracted infusional 5-fluorouracil and weekly carboplatin showed a 17% overall objective response rate, with two complete and seven partial responses.

The treatment regimen demonstrated a median overall survival of 22 weeks, with a notably low rate of serious toxicities, making it a potentially safer alternative to other combination therapies for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program Study. Auerbach, M., Wampler, GL., Lokich, JJ., et al.[2020]

In a phase II study involving 29 patients with advanced pancreatic cancer, the combination of gemcitabine and protracted 5-fluorouracil showed a 10% partial response rate and a 42% stabilization rate, with a median disease control duration of 5.6 months.

The treatment was generally well tolerated, with myelosuppression being the main side effect, but no severe (grade 4) toxicities were reported, indicating a manageable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and protracted 5-FU for advanced pancreatic cancer. A phase II study. Kurtz, JE., Kohser, F., Négrier, S., et al.[2022]

References

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

Tumor-Specific Delivery of 5-Fluorouracil-Incorporated Epidermal Growth Factor Receptor-Targeted Aptamers as an Efficient Treatment in Pancreatic Ductal Adenocarcinoma Models. [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experience with chemotherapy for advanced pancreatic carcinoma]. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients with advanced adenocarcinoma of the pancreas. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer. [2018]

5. Greece pubmed.ncbi.nlm.nih.gov

Cisplatin, 5-Fluorouracil, and leucovorin in the therapy of adenocarcinomas of the pancreas. [2019]

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

Review of a new antimetabolic agent 1-hexylcarbamoyl-5-fluorouracil (HCFU). [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

First-line treatment of pancreatic cancer patients with the combination of 5-fluorouracil/folinic acid plus gemcitabine: a multicenter phase II trial by the CONKO-study group. [2022]

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

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial. [2019]

10. France pubmed.ncbi.nlm.nih.gov

[Continuous double administration of 5 fluorouracil (intravenous and intraperitoneal) modulated by folinic acid: phase I clinical study and pharmacokinetics in patients with intra-abdominal developing cancers]. [2013]

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

[Possibilities of palliation in pancreatic cancer]. [2017]

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

Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program Study. [2020]

13. Greece pubmed.ncbi.nlm.nih.gov

Gemcitabine and protracted 5-FU for advanced pancreatic cancer. A phase II study. [2022]