Glufosfamide vs Fluorouracil for Pancreatic Cancer

Recruiting at 19 trial locations

Overseen By Edwin Thomas

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eleison Pharmaceuticals LLC.

Must not be taking: Antibiotics, Insulin

Disqualifiers: Diabetes, Brain metastases, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3-6 months

480 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if glufosfamide can extend the lives of people with metastatic pancreatic cancer compared to the standard treatment with fluorouracil (5-FU). It targets patients whose cancer has spread and who have not responded to a gemcitabine-based treatment. Participants will receive either glufosfamide or 5-FU to evaluate which is more effective. The trial seeks individuals with pancreatic cancer that has spread and who have experienced disease progression during or after gemcitabine treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that glufosfamide has been tested in people with pancreatic cancer. Earlier studies found that it could shrink tumors or stop their growth in some cases. However, like many cancer treatments, it can cause side effects. In past trials, glufosfamide was generally well-tolerated, but some patients experienced low blood cell counts and nausea. It's important to weigh these potential risks against the benefits.

Fluorouracil (5-FU) is a well-known treatment used for many years to treat various cancers, with its safety well-documented. Common side effects include mouth sores, low blood cell counts, and nausea. It is generally considered safe when used as directed by healthcare professionals.

Both treatments have their own side effects, so individuals considering joining a trial should discuss all potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Unlike the standard chemotherapy options for pancreatic cancer, which often include drugs like gemcitabine or nab-paclitaxel, glufosfamide offers a unique approach by using a novel active ingredient. Glufosfamide is a derivative of glucose, designed to exploit the high glucose uptake of cancer cells, delivering the chemotherapy directly where it's needed most. This targeting mechanism has the potential to enhance effectiveness while minimizing damage to healthy cells. Researchers are excited about glufosfamide because it could offer a more targeted and potentially less toxic alternative to traditional treatments, paving the way for better outcomes in pancreatic cancer care.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will compare the effectiveness of glufosfamide and fluorouracil (5-FU) in treating pancreatic cancer. Research has shown that glufosfamide may reduce tumor size, with some patients experiencing a complete response, meaning their cancer disappeared. This suggests glufosfamide could be effective.

Fluorouracil, also known as 5-FU, is another treatment option in this trial. It is a common cancer treatment that stops cancer cells from growing and is a standard treatment for several types of cancer, including pancreatic cancer. Both treatments have been studied, and evidence supports their use against pancreatic cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Edwin Thomas

Principal Investigator

Eleison Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Glufosfamide

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

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

Approved in European Union as 5-Fluorouracil for:

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

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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 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]

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 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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15801867/

Glufosfamide: beta-D-Glc-IPM, D 19575 Threshold received fast-track status for glufosfamide from the US FDA in the treatment of metastatic pancreatic cancer refractory to gemcitabine in November ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00005053

Glufosfamide With or Without Hydration in Treating Patients ... PURPOSE: Randomized phase II trial to compare the effectiveness of glufosfamide with or without hydration in treating patients who have pancreatic cancer that ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2000.18.20.3535

Phase I Trial of 6-Hour Infusion of Glufosfamide, a New ... There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1950432/

A Novel Alkylating Agent, Glufosfamide, Enhances the ... A recent study has suggested that gemcitabine may be more effective as adjuvant therapy after complete surgical resection of pancreatic cancer and may increase ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=98f583f2-1e18-48f8-84fa-c8b0ec7d5637

glufosfamide (D 19575) / Eleison Pharma ... data from Eleison's ongoing Phase 3 trial and previous clinical studies of glufosfamide, an investigational treatment for pancreatic cancer. The platform ...