Clinical trial NCT00440167: Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine
Official title: Randomized Phase III Trial With Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine in Patients With Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: capecitabine
gemcitabine
Erlotinib
pancreatic cancer
advanced
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2007-02-26
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: TTF2
timeFrame: approximate 6 months after first line treatment
Secondary outcomes:
measure: TTF1
timeFrame: approximate 6 months after randomization
measure: Remission Rate
timeFrame: approximate 6 months after randomization
measure: Overall Survival
timeFrame: 42 months after randomization
measure: Clinical Benefit Response
timeFrame: approximate 6 months after randomization
measure: Tumor marker CA19-9 characteristics
timeFrame: approximate 6 months after randomization
measure: Quality of Life
timeFrame: approximate 6 months after randomization
measure: Toxicity
timeFrame: approximate 6 months after randomization
Other outcomes:
Locations:
Study officials:
affiliation: University of Munich - Klinikum Grosshadern
name: Volker Heinemann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.