Uracil and ftorafur (UFT) and radiotherapy in patients with locally advanced pancreatic cancer

A multicentre randomised phase II clinical study of uracil and ftorafur (UFT) and radiotherapy with or without cetuximab following induction gemcitabine plus capecitabine in patients with locally advanced pancreatic cancer

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN65518365

Enrollment

Registered

2010-10-04

Start date

2009-03-01

Completion date

Unknown

Last updated

2016-10-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally advanced pancreatic cancer Cancer Pancreatic cancer

Interventions

1. Neoadjuvant gemcitabine and capecitabine: 1.1. Gemcitabine 100 mg/m2 intravenous (iv) infusion over 30 minutes, the lyophilised powder being diluted in normal saline. Administered on days 1, 8 and

30 days in total) 2.1.2. Leucovorin 90 mg/day in 3 divided doses days 1 - 42 (on days of RT only

30 days in total) 2.1.3. Radiotherapy 54 Gy in 30 fractions over 6 weeks 2.2. Arm B: uracil and ftorafur (UFT) plus cetuximab plus radiotherapy - 2.2.1. Cetuximab 400 mg/m2 (first dose) day 1 then 250

30 days in total) 2.2.3. Leucovorin 90 mg/day in 3 divided doses days 1 - 42 (on days of RT only

30 days in total) 2.2.4. Radiotherapy 54 Gy in 30 fractions over 6 weeks 3. Post chemoradiation gemcitabine and capecitabine: The same treatment schedule should be used as neo-adjuvant gemcitabine an

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Aged greater than or equal to 18 years, either sex 2. Histological or cytological diagnosis of adeno- or undifferentiated non-small cell carcinoma of pancreas 3. Considered to be unresectable based on at least one of the following: 3.1. Extensive peri-pancreatic lymph node involvement 3.2. Encasement or occlusion of the superior mesenteric vein (SMV) or SMV/portal vein confluence 3.3. Direct involvement of superior mesenteric artery (SMA), coeliac axis, inferior vena cava (IVC) or aorta 4. World Health Organization (WHO) performance status 0 - 2 5. No evidence of metastatic disease as determined by computed tomography (CT) scan (chest, abdomen and pelvis) or other investigations 6. Adequate bone marrow function with platelets greater than or equal to 100 x 10^9/l, white blood cells (WBC) greater than or equal to 3 x 10^9/l and neutrophils greater than or equal to 1.5 x 10^9/l 7. Serum bilirubin less than 1.5 x upper limit of institutional normal range (ULN) and transaminases less than or equal to 2.5 x ULN 8. Calculated/measured glomerular filtration rate (GFR) greater than or equal to 50 ml/min (either calculated by Cockcroft and Gault formula or measured as per usual local procedure) 9. No concurrent uncontrolled medical condition 10. No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last 10 years 11. Life expectancy greater than 3 months 12. Adequate contraceptive precautions if relevant 13. Informed written consent

Exclusion criteria

Exclusion criteria: 1. Medical or psychiatric conditions that compromise the patient's ability to give informed consent 2. Presence of metastatic disease 3. Concurrent uncontrolled medical conditions 4. Any previous chemotherapy or radiotherapy, and any investigational treatment for advanced pancreatic cancer 5. Adjuvant chemotherapy with fluoropyrimidine or gemcitabine within 12 months of trial entry 6. Adjuvant radiotherapy with or without chemotherapy for pancreatic cancer 7. Pregnancy or breast feeding 8. Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract 9. Patients with a known hypersensitivity to 5-FU or with a dihydropyrimidine dehydrogenase (DPD) deficiency 10. Clinically significant (i.e. active) cardiovascular disease. This includes, but is not limited to, the following examples: 10.1. Cerebrovascular accidents (less than or equal to 6 months prior to registration) 10.2. Myocardial infarction (less than or equal to 1 year prior to registration) 10.3. Uncontrolled hypertension (greater than 150/100 mmHg) while receiving chronic medication 10.4. Unstable angina 10.5. New York Heart Association (NYHA) Grade II or greater congestive heart failure 10.6. Serious cardiac arrhythmia requiring medication 10.7. Clinically significant electrocardiogram (ECG) findings (e.g. QTc greater than or equal to 440 msecs [male] 460 msecs [female] or greater than or equal to 2º AV Block, etc.). Patients who suffer from serious cardiac arrhythmia requiring medication can enter the study only if they are considered to be in a stable condition regarding both the arrhythmia and their medication. Patients with pacemakers are allowed to enter the study only if they are considered as being in a stable condition. In case of doubt, the investigator should obtain a consultation with a local cardiologist.

Design outcomes

Primary

Measure	Time frame
One-year overall survival rate	—

Secondary

Measure	Time frame
1. Radiological response evaluation: CT thorax, abdomen and pelvis after neo-adjuvant chemotherapy before randomisation and 6 weeks after completion of chemoradiation. Responses will be assessed in accordance with the Response Evaluation Criteria for Solid Tumours (RECIST). 2. Tumour marker CA19-9: this will be measured at baseline and four weekly during neo-adjuvant chemotherapy, at randomisation and 6 weeks after completion of chemoradiation, and thereafter at each clinic follow-up appointment. 3. Progression free survival (PFS): 3.1. PFS-registration will be measured from date of registration to date of first appearance of disease progression, relapse, or death from any cause; patients alive without progression or relapse will be censored at date last known to be alive. 3.2. PFS-randomisation will be measured from date of randomisation to date of first appearance of disease progression, relapse, or death from any cause; patients alive without progression or relapse will be censored at date last known to be alive. 4. Overall survival: this will be measured from date of registration to date of death from any cause; surviving patients will be censored at date last known to be alive. 5. Toxicity: this will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 during neo-adjuvant chemotherapy and during chemoradiation. Late radiotherapy toxicity (greater than 12 months after treatment) will be assessed using CTCAE version 3.0. 6. Quality of life: this will be evaluated using the EORTC QLQ C30 (Version 3) and PAN26 module. It will be evaluated at baseline, at 12 weeks (after neo-adjuvant chemotherapy) and at 24 weeks (6 weeks after chemoradiation). It will then be evaluated three monthly during year 1, six monthly during the years 2 and 3 and annually for years 4 and 5.	—

Measure

Time frame

1. Radiological response evaluation: CT thorax, abdomen and pelvis after neo-adjuvant chemotherapy before randomisation and 6 weeks after completion of chemoradiation. Responses will be assessed in accordance with the Response Evaluation Criteria for Solid Tumours (RECIST). 2. Tumour marker CA19-9: this will be measured at baseline and four weekly during neo-adjuvant chemotherapy, at randomisation and 6 weeks after completion of chemoradiation, and thereafter at each clinic follow-up appointment. 3. Progression free survival (PFS): 3.1. PFS-registration will be measured from date of registration to date of first appearance of disease progression, relapse, or death from any cause; patients alive without progression or relapse will be censored at date last known to be alive. 3.2. PFS-randomisation will be measured from date of randomisation to date of first appearance of disease progression, relapse, or death from any cause; patients alive without progression or relapse will be censored at date last known to be alive. 4. Overall survival: this will be measured from date of registration to date of death from any cause; surviving patients will be censored at date last known to be alive. 5. Toxicity: this will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 during neo-adjuvant chemotherapy and during chemoradiation. Late radiotherapy toxicity (greater than 12 months after treatment) will be assessed using CTCAE version 3.0. 6. Quality of life: this will be evaluated using the EORTC QLQ C30 (Version 3) and PAN26 module. It will be evaluated at baseline, at 12 weeks (after neo-adjuvant chemotherapy) and at 24 weeks (6 weeks after chemoradiation). It will then be evaluated three monthly during year 1, six monthly during the years 2 and 3 and annually for years 4 and 5.

—

Countries

United Kingdom

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026