Comparison of chemotherapy with radiochemotherapy as treatment of patients with locally advanced, primarily inoperable pancreatic carcinoma

Phase 1

• Conditions: locally advanced, primarily inoperable pancreatic carcinoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-001850-24-AT
• Lead Sponsor: ABCSG (Austrian Breast & Colorectal Cancer Study Group)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-07-18
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Informed consent signed prior to randomization and prior to any study specific procedure
• Patients with histologically proven PDAC, classified as locally advanced, primarily inoperable disease;
• patients with suspicious peripancreatic lymph nodes at initial staging, accessible by surgery are included in the study
• Tumor must have at least one diameter of 15 mm assessed with conventional imaging techniques (e.g. CT, MRI) and at least on diameter of 10 mm measured by contrast enhanced CT
• Patients scheduled for neoadjuvant treatment by the interdisciplinary tumor board
• Radiologically determinable disease defined by RECIST version 1.1 within 4 weeks prior to randomization
• ECOG performance status =1 or Karnofsky =70%
• Adequate hematologic function, as follows (= 7d prior to randomization):
o absolute neutrophil count (ANC) =1.5 x 109/L (in case ANC is not routinely measured, as alternatively relative neutrophil count > 50% is acceptable)
o white blood cell count (WBC) = 3.0 x 109/L
o platelet count = 100 x 109/L
o haemoglobin = 9 x g/dL
• Adequate renal function, as follows (= 7d prior to randomization):
o creatinine = 1.5 x upper limit of normal (ULN) or GFR >50mL/min
• Adequate hepatic function, as follows (= 7d prior to randomization):
o aspartate aminotransferase (ASAT) = 5 x ULN
o alanine aminotransferase (ALAT) = 5 x ULN
o total bilirubin = 1.5 x ULN
• Any age = 18 = 75 years
• Ability to comply with the protocol and attend follow up
• Women of childbearing potential must have a negative serum pregnancy test done within 1 week prior to study drug administration. Women are not considered of childbearing potential in case that the following criteria applies:
o after having undergone hysterectomy and/or bilateral ovarectomy and/or bilateral tubal ligation
o = 60 years
o with FSH and E2 in the postmenopausal range
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112

Exclusion Criteria

• External biliary drain (Common bile duct stenting allowed)
• Major surgery within 4 weeks prior to start of study treatment
• Any past or current history of other malignancies (except in situ carcinoma, non-metastatic non-melanomatous skin cancers) less than 2 years prior to randomization
• Any radiological suspicion, or histological proof of distant metastases or extra-pancreatic disease other than regional lymph node enlargement at initial staging
• Any chemo- or radiotherapy for PDAC prior to study inclusion
• Concurrent or prior systemic antitumor therapy within the last 2 years
• Active infection requiring systemic treatment or any uncontrolled infections < 14 days prior to randomization
• Concurrent administration of other IMP during treatment phase
• Concurrent participation in another clinical trial with the same primary endpoint
• Pregnancy, lactation, women of childbearing potential not willing to use effective means of contraception until 6 months after completion of study treatment
• Male patients not willing to use effective means of contraception until three months after completion of study treatment
• Previous irradiation within the actual fields of planned radiotherapy
• Any known hypersensitivity/allergic reaction to any of the components of study treatments
• Any severe and/or uncontrolled medical conditions including but not limited to:
o Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 12 months prior to enrolment, serious uncontrolled cardiac arrhythmia
o Acute and/or chronic, active infectious disorders and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study therapy
o Active disorders of skin and/or mucosa and/or ocular and/or GI disorders > Grade 1
o Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, risk associated with study participation or IMP administration, or which, in the judgment of the investigator, would make the patient inappropriate for this study participation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that in patients suffering from a primarily inoperable LAPC neoadjuvant chemotherapy followed by concurrent neoadjuvant radiochemotherapy is superior to neoadjuvant chemotherapy alone in terms of R0-resectability;Secondary Objective: To demonstrate superior efficacy of neoadjuvant chemotherapy followed by concurrent neoadjuvant radiochemotherapy to neoadjuvant chemotherapy alone with respect to tumor response, histo-pathological tumor response, progression-free survival (PFS) and/or disease-free survval (DFS) and overall survival (OS), toxicity, perioperative complications, radiochemotherapy quality assurance;Primary end point(s): Histological R0 resection rate in the IIT population;Timepoint(s) of evaluation of this end point: Surgery<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Tumor response measured by RECIST criteria<br>• Histo-pathological tumor response with respect to proportion of severely degenerative cancer cells<br>• DFS as time from surgery to PDAC recurrence in R0 patients<br>• PFS as time from randomization until disease progression<br>• OS as time from randomization to death from any cause<br>• occurrence of treatment related toxicities<br>• perioperative complications classified according to Clavien and Dindo<br>• total duration and interruptions of concurrent neoadjuvant radiochemotherapy, total dose of the radiotherapy and administration of concomitant chemotherapy;Timepoint(s) of evaluation of this end point: • Tumor response, histo-pathological tumor response, perioperative complications, toxicities: after neoadjuvant treatment and surgery<br>• DFS, PFS, OS: after last patient had last FU-Visit<br>