Pancreatic Carcinoma: Chemoradiation Compared With Chemotherapy Alone After Induction Chemotherapy

NCT ID: NCT01827553

Last Updated: 2024-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 830 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-04
• Study Completion Date: 2023-11-08

Brief Summary

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction CT, chemoradiotherapy

Induction chemotherapy with gemcitabine or FOLFIRINOX; Radiotherapy, 28 x 1.8 Gy; Chemotherapy, gemcitabine;

Group Type: EXPERIMENTAL

Induction chemotherapy with gemcitabine or FOLFIRINOX

Intervention Type: DRUG

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)

Radiotherapy, 28 x 1.8 Gy

Intervention Type: RADIATION

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.

Chemotherapy, gemcitabine

Intervention Type: DRUG

5 cycles of 300 mg/m\^2/d gemcitabine infusions and than 3 administrations of 1000 mg/m\^2/d

Induction CT, chemotherapy

Induction chemotherapy with gemcitabine or FOLFIRINOX; Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy

Group Type: ACTIVE_COMPARATOR

Induction chemotherapy with gemcitabine or FOLFIRINOX

Intervention Type: DRUG

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)

Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy

Intervention Type: DRUG

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

Interventions

Induction chemotherapy with gemcitabine or FOLFIRINOX

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)

Intervention Type: DRUG

Radiotherapy, 28 x 1.8 Gy

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.

Intervention Type: RADIATION

Chemotherapy, gemcitabine

5 cycles of 300 mg/m\^2/d gemcitabine infusions and than 3 administrations of 1000 mg/m\^2/d

Intervention Type: DRUG

Chemotherapy with gemcitabine or FOLFIRINOX according to induction chemotherapy

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

Intervention Type: DRUG

Other Intervention Names

all brands of gemcitabine and FOLFIRINOX components are allowed; all brands of gemcitabine are allowed; all brands of gemcitabine and FOLFIRINOX components are allowed

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainer Fietkau, MD

Role: PRINCIPAL_INVESTIGATOR

Strahlenklinik, Universitätsklinikum Erlangen

Locations

Bayreuth, Klinikum

Bayreuth, , Germany

Bochum, Augusta-Kranken-Anstalt, Hämatologie/Onkologie

Bochum, , Germany

Bochum, St. Josef-Hospital

Bochum, , Germany

Köln Universitätsklinikum

Cologne, , Germany

Dresden Onkologische Gemeinschaftspraxis

Dresden, , Germany

Erlangen Universitätsklinikum

Erlangen, , Germany

Frankfurt/Main Universitätsklinikum

Frankfurt am Main, , Germany

Freiburg Universitätsklinikum

Freiburg im Breisgau, , Germany

Göttingen Universitätsmedizin

Göttingen, , Germany

Halle St. Elisabeth und St. Barbara Krankenhaus

Halle, , Germany

Heilbronn SLK-Kliniken

Heilbronn, , Germany

Jena Universitätsklinikum

Jena, , Germany

Leer MVM

Leer, , Germany

Leipzig UCCL

Leipzig, , Germany

Magdeburg Universitätsklinikum

Magdeburg, , Germany

Magdeburg Klinikum

Magdeburg, , Germany

Mannheim Universitätsmedizin

Mannheim, , Germany

München Großhadern LMU

München, , Germany

Münster Universitätsklinikum

Münster, , Germany

Oldenburg Pius Hospital

Oldenburg, , Germany

Regensburg Krankenhaus Barmherzige Brüder

Regensburg, , Germany

Regensburg Universitätsklinikum

Regensburg, , Germany

Würzburg CCC Mainfranken

Würzburg, , Germany

Countries

Germany

References

Fietkau R, Ghadimi M, Grutzmann R, Wittel UA, Jacobasch L, Uhl W, Croner RS, Bechstein WO, Neumann UP, Waldschmidt D, Boeck S, Moosmann N, Reinacher-Schick AC, Golcher H, Adler W, Semrau S, Lubgan D, Kallies A, Hecht M, Tischoff I, Tannapfel A, Frey B, Oettle H; CONKO Study Group. Benefit of Chemoradiotherapy Versus Chemotherapy After Induction Therapy for Conversion of Unresectable Into Resectable Pancreatic Cancer: The Randomized CONKO-007 Trial. J Clin Oncol. 2025 Oct 20;43(30):3266-3278. doi: 10.1200/JCO-24-01502. Epub 2025 Aug 13.

Reference Type: DERIVED

PMID: 40802908 (View on PubMed)

Wittel UA, Lubgan D, Ghadimi M, Belyaev O, Uhl W, Bechstein WO, Grutzmann R, Hohenberger WM, Schmid A, Jacobasch L, Croner RS, Reinacher-Schick A, Hopt UT, Pirkl A, Oettle H, Fietkau R, Golcher H. Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial. BMC Cancer. 2019 Oct 22;19(1):979. doi: 10.1186/s12885-019-6148-5.

Reference Type: DERIVED

PMID: 31640628 (View on PubMed)

Other Identifiers

2009-014476-21

Identifier Type: -

Identifier Source: org_study_id