Glufosfamide vs Fluorouracil for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+19 other 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.
12345Is 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.
678910What 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.
12111213Eligibility 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
I agree to use effective contraception during and for 6 months after the study.
My pancreatic cancer was confirmed through a biopsy.
I am 18 years old or older.
I am fully active or can carry out light work.
My cancer has spread from the pancreas to other parts of my body.
My condition worsened despite treatment with gemcitabine.
Exclusion Criteria
I had major surgery less than 3 weeks ago and haven't fully recovered.
I am currently taking antibiotics for a serious infection.
I cannot or do not want to have multiple CT scans.
I have had more than one treatment for my metastatic pancreatic cancer.
I have brain metastases but do not show symptoms.
I am HIV positive or have active hepatitis B or C.
My kidney function, measured by creatinine clearance, is below 60 mL/min.
I am not pregnant or breastfeeding.
I have had serious heart problems or symptoms in the last year.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: glufosfamideExperimental Treatment1 Intervention
Glufosfamide: 4500 mg/m2 IV over 6 hours on Day 1 of each 21-day cycle
Group II: 5-FUActive Control1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Saint Louis University Cancer CenterSaint Louis, MO
Comprehensive Cancer Care Medical Group, Inc.Corona, CA
Compassionate Care Research Group, Inc.Fountain Valley, CA
McFarland Clinic OncologyAmes, IA
More Trial Locations
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Who is running the clinical trial?
Eleison Pharmaceuticals LLC.Lead Sponsor
References
Tumor-Specific Delivery of 5-Fluorouracil-Incorporated Epidermal Growth Factor Receptor-Targeted Aptamers as an Efficient Treatment in Pancreatic Ductal Adenocarcinoma Models. [2022]Fluoropyrimidine c (5-fluorouracil [5FU]) increasingly represents the chemotherapeutic backbone for neoadjuvant, adjuvant, and palliative treatment of pancreatic ductal adenocarcinoma (PDAC). Even in combination with other agents, 5FU efficacy remains transient and limited. One explanation for the inadequate response is insufficient and nonspecific delivery of 5FU to the tumor.
[Experience with chemotherapy for advanced pancreatic carcinoma]. [2022]The effectiveness of different regimens of chemotherapy for advanced pancreatic cancer was compared in 74 cases (1995-1999). 5-fluorouracil (5FU), adriamycin and mitomycin C (FAM) were given to 12 patients, 5FU alone--23, 5FU plus leukovorin--29, and gemcitabine alone--10. Metastases to the liver were detected in 42 (57%) patients. Partial response (40) was registered in: FAM--1 (8%); 5FU--1 (4%); 5FU + leukovorin--3 (10%); gemcitabine--3 (30%). Mean duration (40) was 5.4; 4; 6.1 and 9 months, respectively. Stabilization was recorded in 17 (23%), mean duration--4.4 months; tumor progression--49 (66%). Toxic side-effects of all the regimens were insignificant. Mean survival rates following FAM, 5FU, 5FU + leukovorin were 4.4; 4.2 and 5.6 months, respectively, while that for gemcitabine varied 3-24 months (on average--7.9 months). Survival in patients responsive to chemotherapy was 9.8; remaining patients--4.7 (p (0.05). Chemotherapy for advanced pancreatic carcinoma is a measure of palliation; its use was followed by a 20% increase in survival. Gemcitabine treatment appeared most effective.
Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients with advanced adenocarcinoma of the pancreas. [2020]In advanced adenocarcinoma of the pancreas treatment with 5-fluorouracil (5-FU) or ifosfamide results in response rates of approximately 20%. Continuous infusion of these drugs is on many grounds theoretically attractive and may therefore offer advantages over bolus or short-term infusion.
Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer. [2018]Continuous venous infusion of 5-fluorouracil (5FU) was investigated in 18 patients with measureable advanced cancer of the pancreas. 5FU was given for 7 days in a dose of 500 mg/m2 by continuous venous infusion over a 24-hour period and then followed by a dose of 170 mg/m2 for more than 28 days. Ten patients had no change including 1 patient with minor response, and 4 patients had disease progression. Serum CA19-9 levels were measured serially after chemotherapy in 13 of 14 evaluable patients. In 3 of 10 patients who showed high levels before treatment, serum CA19-9 levels were significantly decreasing after treatment.
Cisplatin, 5-Fluorouracil, and leucovorin in the therapy of adenocarcinomas of the pancreas. [2019]Pancreatic cancer is resistant to most chemotherapeutic regimens. Based upon evidence of synergy between 5-fluorouracil (5-FU) and cisplatin (CDDP), and of enhanced 5-FU activity in the presence of leucovorin in other neoplasms, a phase II study of CDDP, 5-FU, and leucovorin was conducted to determine the efficacy of this regimen in patients with unresectable adenocarcinomas of the pancreas. Nineteen patients were enrolled, and all were evaluable for toxicity and response. One complete and two partial responses were observed (15.8%). Adverse effects were reversible and tolerable. This regimen has limited activity against pancreatic cancer, and cannot be recommended as standard therapy in this disease.
Review of a new antimetabolic agent 1-hexylcarbamoyl-5-fluorouracil (HCFU). [2021]A new 5-fluorouracil (5-FU) derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU), has been developed in the National Cancer Center, and its phase I study is being performed in Japan by a clinical study group involving major institutions. Its LD 50 values are nearly equal to those of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and greater than those of 5-FU, and this compound is more effective than the latter two analogues against various experimental murine tumor systems. In the phase I study, the incidence ratio of side effects was dose dependent, and the characteristic subjective symptoms were hot sensation and pollakisuria. No hematologic or serum biochemical changes were noted.
[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]The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.
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]This open-label, multi-center phase II study investigated the efficacy and safety of the combination of 5-fluorouracil (5-FU)/folinic acid (FA) plus gemcitabine (GFF) in patients with advanced pancreatic cancer. The study is based on our completed dose finding phase I trial.
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]A phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil (5-FU), leucovorin, and inteferon alpha-2a in metastatic pancreatic carcinoma. Twenty-three patients were entered in this study. Four patients withdrew before receiving treatment and one patient was nonevaluable for response because of treatment-related toxicity. The most common significant toxicity was nausea and vomiting. Treatment-related hospitalization was significant. Of 18 evaluable patients, 4 maintained stable disease and 14 had disease progression. None had an objective clinical response. We conclude that this biochemically modulated 5-FU regimen is ineffective treatment for advanced pancreatic carcinoma, with significant toxicity even in highly selected patients with an ambulatory performance status.
[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]Thirteen patients with intra-abdominal malignancies entered a phase I study of fluorouracil (5-FU) given by continuous infusion (96 h) iv and ip, simultaneously, and modulated by high-dose folinic acid-iv. Severe but reversible stomatitis was the only dose-limiting toxicity at a dose of 5-FU of 550 mg/m2/day. Local toxicity (5-FU-induced abdominal pain) was a significant side effect in patients receiving more than 1 cycle. The pharmacokinetic advantage of 5-FU-ip was confirmed in our study (ratio AUC peritoneum/plasma between 160 and 328). The systemic exposure to 5-FU (plasmatic AUC ranging from 73.4 to 173.21 microM) and to AF were found in efficacious ranges. The recommended dose of 5-FU iv and ip is 500 mg/m2/day. This regimen is feasible and may potentially have application for adjuvant chemotherapeutic programs after surgery for colorectal cancer.
[Possibilities of palliation in pancreatic cancer]. [2017]Adenocarcinoma of the pancreas is the cause of 3-4% of cancer related deaths in Italy and over 80% of all patients exhibit advanced disease. Treatment with surgery and chemio-radiotherapy may have meaningful results in resectable and locoregional tumours respectively. Chemotherapy is the treatment of choice in metastatic disease as palliative intent, although pancreatic tumour is considered resistant to treatment with conventional cytotoxicity drugs. Assessment of response of primary tumor is extremely difficult because of its anatomical location and fibrotic reaction around the tumor. Furthermore, medical problems associated with the age of patients, reduced performance status (PS), mainourished conditions, jaundice and pain, limit patients' tolerance and response to chemotherapy. 5-fluorouracil (5-FU) is the most frequently used drug in the treatment of pancreatic cancer with a RR of 28% in the trials performed in mid 1980, while more recently studies have reported a RR of 5-15%. Biochemical modulation of 5-FU by leucovorin, PALA and interferon does not appear to produce better results than 5-FU alone. 5-FU-based combination chemotherapy (FAM, SMF, etc) have shown interesting results in phase II (30-40%), but in a randomized trial the results of combination were similar to 5-FU alone (
Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program Study. [2020]Advanced pancreatic cancer is a rapidly fatal disease whose course has been little influenced by chemotherapy. Earlier studies have shown some modest promise for the combination of protracted infusional 5-fluorouracil (PIF) and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity, PIF plus weekly carboplatin.
Gemcitabine and protracted 5-FU for advanced pancreatic cancer. A phase II study. [2022]Although chemotherapy in advanced pancreatic cancer procures dismal results, both 5-fluorouracil and gemcitabine have shown a modest activity. We report a phase II study of gemcitabine combined with protracted 5-fluorouracil.