Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine

Randomized Phase III Trial With Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine in Patients With Advanced Pancreatic Cancer

This crossover trial is performed in advanced and metastatic pancreatic cancer not previously exposed to chemotherapy. The study compares a standard arm with gemcitabine plus erlotinib to an experimental arm with capecitabine plus erlotinib. It is the first trial of its kind to incorporate second-line treatment into the study design. Patient who fail on first-line therapy are switched to the comparator chemotherapy without erlotinib. The trial therefore not only compares two different regimens of first-line treatment, it also compares two sequential treatment strategies.

Study Overview

• Status: Unknown
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Erlotinib; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 75 years
• Histologically proven pancreatic cancer stage III or IV (T1-3 N1M0 or T1 3N0 1M1)
• No option for resection with curative intent
• At least one measurable or not measurable lesion (according to RECIST)
• No previous chemotherapy or other systemic tumor therapy
• No previous radiation
• Performance-Status 0-2 according to WHO/ECOG
• Life expectancy of at least 3 months
• Adequate kidney-, liver- and bone marrow function, defined as
• Absolute neutrophil count * 1,5 x 109/l
• Hemoglobin * 8 g/dl
• Thrombocytes * 100 x 109/l
• Bilirubin * 2 x upper norm (with liver mets < 5-fold)
• Serum Creatinine * 1,25 x upper norm
• Creatinine clearance > 30 ml/min (Cockroft/Gault)
• Transaminases * 2,5 x upper norm (with liver mets < 5-fold)
• Possibility of regular long-term follow-up
• Negative pregnancy test in women at childbearing age
• All patients must have signed an informed consent before study entry.

Exclusion Criteria:

• Known secondary cancer other than curatively treated basalioma or carcinoma in situ of the cervix uteri
• Clinically unstable CNS-metastases
• Known hypersensitivity against study medication
• Severe impairment of renal function (creatinine clearance < 30 ml/min)
• Severe impairment of liver function (bilirubin > 2,0 x above upper norm, transaminases > 2,5 x upper norm, or with known liver metastasis >5 x upper norm)
• Clinically relevant disease of the cardiovascular system or other vital organs
• Known polyneuropathy
• Known DPD-deficiency (screening not required)
• Simultaneous treatment with the antiviral agent sorivudin or chemically related agents such as brivudin
• Pregnancy, lactation or lack of reliable contraception in women at childbearing age
• Mental disease, drug- or alcohol abuse
• Participation in another clinical trial within the last 4 weeks
• All other diseases which may prevent adequate participation in the trial
• Indication of lack of compliance with study regulations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A	Drug: Capecitabine; Capecitabine 2 x 1000 mg/m²/ d oral, d 1 - 14 followed by 7 days Pause ("Flat Dosing"); Drug: Erlotinib; Erlotinib 150 mg/d oral, daily without break
Active Comparator: Arm B	Drug: Erlotinib; Erlotinib 150 mg/d oral, daily without break; Drug: Gemcitabine; Gemcitabine 1000 mg/m², d 1, 8 , 15, q d28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTF2	Time to treatment failure, after 2nd line (crossover) therapy	approximate 6 months after first line treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTF1	Time to treatment failure	approximate 6 months after randomization
Remission Rate		approximate 6 months after randomization
Overall Survival		42 months after randomization
Clinical Benefit Response		approximate 6 months after randomization
Tumor marker CA19-9 characteristics		approximate 6 months after randomization
Quality of Life		approximate 6 months after randomization
Toxicity		approximate 6 months after randomization

Collaborators and Investigators

• Sponsor: PD Dr. med. Volker Heinemann
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Volker Heinemann, MD, University of Munich - Klinikum Grosshadern

Publications and helpful links

General Publications

• Guenther M, Haas M, Heinemann V, Kruger S, Westphalen CB, von Bergwelt-Baildon M, Mayerle J, Werner J, Kirchner T, Boeck S, Ormanns S. Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer - translational results from the AIO-PK0104 Phase 3 study. Br J Cancer. 2020 Oct;123(9):1370-1376. doi: 10.1038/s41416-020-01029-7. Epub 2020 Aug 24. Erratum In: Br J Cancer. 2021 Aug;125(3):466.
• Ormanns S, Siveke JT, Heinemann V, Haas M, Sipos B, Schlitter AM, Esposito I, Jung A, Laubender RP, Kruger S, Vehling-Kaiser U, Winkelmann C, Fischer von Weikersthal L, Clemens MR, Gauler TC, Marten A, Geissler M, Greten TF, Kirchner T, Boeck S. pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104. BMC Cancer. 2014 Aug 28;14:624. doi: 10.1186/1471-2407-14-624.
• Heinemann V, Vehling-Kaiser U, Waldschmidt D, Kettner E, Marten A, Winkelmann C, Klein S, Kojouharoff G, Gauler TC, von Weikersthal LF, Clemens MR, Geissler M, Greten TF, Hegewisch-Becker S, Rubanov O, Baake G, Hohler T, Ko YD, Jung A, Neugebauer S, Boeck S. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9. doi: 10.1136/gutjnl-2012-302759. Epub 2012 Jul 7.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): December 1, 2011
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: February 22, 2007
• First Submitted That Met QC Criteria: February 22, 2007
• First Posted (Estimate): February 26, 2007

Study Record Updates

• Last Update Posted (Estimate): July 9, 2012
• Last Update Submitted That Met QC Criteria: July 5, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: capecitabine; Erlotinib; pancreatic cancer; gemcitabine; advanced
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Erlotinib Hydrochloride; Capecitabine
• Other Study ID Numbers: RC-57 crossover