Pancreatic Carcinoma: Chemoradiation Compared With Chemotherapy Alone After Induction Chemotherapy

Study Overview
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Brief Summary
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This randomized trial examines the effectiveness of chemoradiotherapy compared to chemotherapy alone after induction chemotherapy with 3 cycles of gemcitabine or 6 cycles of FOLFIRINOX in patients with locally advanced, non resectable and non-metastatic pancreatic cancer. Chemotherapeutic agent in chemoradiotherapy is gemcitabine administered in 5 cycles, the agent and its administration for sole chemotherapy is determined by induction chemotherapy. Operability of tumor is evaluated at week 11 after randomisation. Patients will be followed for the duration of therapy and for 5 years after the last study treatment. Overall survival at the end of follow up is defined as primary endpoint. Secondary endpoints are tumor-free survival, rate of local recurrence or local progression, rate of distant metastasis, acute and late toxicity of the chemoradiotherapy, quality of life, rate of remission, rate of curative resections (R0) after chemotherapy and chemoradiotherapy. It is planned to include a total number of 830 patients.

Official Title
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Significance of Chemoradiation Following Induction Chemotherapy in Locally Advanced,Unresectable Pancreatic Cancer -a Randomised Phase 3 Trial: Chemoradiation Following Induction Chemotherapy Compared With Chemotherapy Alone

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Induction chemotherapy with gemcitabine or FOLFIRINOX
* Radiation: Radiotherapy, 28 x 1.8 Gy
* Drug: Chemotherapy, gemcitabine
* Drug: Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years histologically confirmed adenocarcinoma of the pancreas no evidence of distant metastasis based on computed tomography of the thorax and abdomen non resectable pancreatic cancer no evidence of peritoneal carcinosis ECOG-performance status ≤ 2 signed study-specific consent form prior to therapy Exclusion Criteria: fertile patients who refuse effective contraception during study treatment synchron second malignant neoplasm except basal cell carcinoma of the skin and carcinoma in situ of the cervix after curative therapy the Inclusion of patients with prior or concurrent malignancy (≤ 5 years prior to enrolment in study) must be discussed chronic inflammatory disease of the intestine known allergic reactions on study medication on-treatment participation on other trials insufficient liver function: Bilirubin > 2,0 mg/dl; SGOT, SGPT, alkaline phosphatase, gGT more than 3 times upper limit of normal (after Stent implantation in case of obstructive jaundice); cirrhosis of the liver Child B and C insufficient bone marrow function: WBC < 3,0 x 10^9/l, Platelets > 100 x 10^9/l serum creatinine > 1,5 mg/dl, creatinin clearance < 60ml/min (or comparable test) preexisting uncontrolled cardiac disease, signs of cardiac failure, or rhythm disturbances requiring therapy, myocardial infarction within the past 6 months, unstable angina pectoris, congestive heart failure, New York Heart Association (NYHA) class III or IV heart disease neurological and/or psychiatric diseases: stroke, dementia, epilepsy, psychosis active intractable or uncontrollable infection, HIV-infection prior radiotherapy or chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction CT, chemoradiotherapy<br>Induction chemotherapy with gemcitabine or FOLFIRINOX; Radiotherapy, 28 x 1.8 Gy; Chemotherapy, gemcitabine; | Drug: Induction chemotherapy with gemcitabine or FOLFIRINOX<br>* According to medical recommendation, induction chemotherapy is performed with gemcitabine (3 cycles a 3 administrations, 1000 mg/m^2/d)or FOLFIRINOX (6 cycles; 1 cycle: oxaliplatin 85 mg/m^2 2 h infusion, folinic acid 400 mg/ m^2 2h infusion completed after 30 min with irinotecan infusion 180 mg/m^2 for 90 minutes, bolus application 5-FU 400 mg/m^2 followed by 46h infusion of 5-FU 2400 mg/m^2)<br>* Other names: all brands of gemcitabine and FOLFIRINOX components are allowed;Radiation: Radiotherapy, 28 x 1.8 Gy<br>* Radiotherapy combined with chemotherapy starts on day 1 of chemotherapy. Radiation volume is restricted to macroscopic visual tumor region. Radiation is performed in 28 fractions with 1.8 Gy resulting in a total dose of 50.4 Gy.<br>Drug: Chemotherapy, gemcitabine<br>* 5 cycles of 300 mg/m^2/d gemcitabine infusions and than 3 administrations of 1000 mg/m^2/d<br>* Other names: all brands of gemcitabine are allowed;|
| Active Comparator: Induction CT, chemotherapy<br>Induction chemotherapy with gemcitabine or FOLFIRINOX; Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy | Drug: Induction chemotherapy with gemcitabine or FOLFIRINOX<br>* According to medical recommendation, induction chemotherapy is performed with gemcitabine (3 cycles a 3 administrations, 1000 mg/m^2/d)or FOLFIRINOX (6 cycles; 1 cycle: oxaliplatin 85 mg/m^2 2 h infusion, folinic acid 400 mg/ m^2 2h infusion completed after 30 min with irinotecan infusion 180 mg/m^2 for 90 minutes, bolus application 5-FU 400 mg/m^2 followed by 46h infusion of 5-FU 2400 mg/m^2)<br>* Other names: all brands of gemcitabine and FOLFIRINOX components are allowed;Drug: Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy<br>* Chemotherapeutic administration started with during induction chemotherapy is continued; Gemcitabine: 3 cycles a 3 administrations of 1000 mg/m^2/d gemcitabine infusions FOLFIRINOX: 6 cycles<br>* Other names: all brands of gemcitabine and FOLFIRINOX components are allowed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor-free survival |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| rate of local recurrence or local progression |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| Rate of distant metastasis |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| Acute and late toxicity of the chemoradiotherapy |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| Rate of remission |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| Rate of curative resections (R0) after chemotherapy and chemoradiotherapy |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 
| Changes in Quality of life |  | Participants will be followed for the duration of therapy and for 5 years after the last study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, chemoradiotherapy, chemotherapy, FOLFIRINOX, gemcitabine