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

• ClinicalTrials.gov Identifier: NCT00440167
• Recruitment Status: Unknown
• First Posted: February 26, 2007
• Last Update Posted: July 9, 2012
• Sponsor: PD Dr. med. Volker Heinemann
• Collaborator: Roche Pharma AG
• Information provided by (Responsible Party): PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich

Tracking Information

• First Submitted Date: February 22, 2007
• First Posted Date: February 26, 2007
• Last Update Posted Date: July 9, 2012
• Study Start Date: June 2006
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2011)

TTF2 [ Time Frame: approximate 6 months after first line treatment ]

Time to treatment failure, after 2nd line (crossover) therapy

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: June 27, 2011)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: Gemcitabine
  Gemcitabine 1000 mg/m², d 1, 8 , 15, q d28
• 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

Study Arms

• Active Comparator: Arm A
  Interventions:

  • Drug: Capecitabine
  • Drug: Erlotinib
• Active Comparator: Arm B
  Interventions:

  • Drug: Gemcitabine
  • Drug: Erlotinib

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: June 27, 2011): 280
• Original Enrollment: Not Provided
• Estimated Study Completion Date: December 2012
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT00440167
• Other Study ID Numbers: RC-57 crossover
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich
• Original Responsible Party: Not Provided
• Current Study Sponsor: PD Dr. med. Volker Heinemann
• Original Study Sponsor: Ludwig-Maximilians - University of Munich
• Collaborators: Roche Pharma AG

Investigators

• Principal Investigator: Volker Heinemann, MD; University of Munich - Klinikum Grosshadern

• PRS Account: Ludwig-Maximilians - University of Munich
• Verification Date: July 2012