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

NCT00440167 | Unknown Phase 3

• 1 other identifier: RC-57 crossover
• Study Type: interventional
• Target: 280
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pancreatic Cancer

Keywords

capecitabine; gemcitabine; Erlotinib; pancreatic cancer; advanced

Outcome Measures

Primary Outcomes (1)

• TTF2

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

  approximate 6 months after first line treatment

Secondary Outcomes (7)

• TTF1

  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

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Drug: Capecitabine; Drug: Erlotinib

Arm B

ACTIVE COMPARATOR

Drug: Gemcitabine; Drug: Erlotinib

Interventions

Gemcitabine DRUG

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

Arm B

Capecitabine DRUG

Capecitabine 2 x 1000 mg/m²/ d oral, d 1 - 14 followed by 7 days Pause ("Flat Dosing")

Arm A

Erlotinib DRUG

Erlotinib 150 mg/d oral, daily without break

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• PD Dr. med. Volker Heinemann: lead
• Roche Pharma AG: collaborator

Related Publications (5)

• Weiss L, Heinemann V, Fischer LE, Gieseler F, Hoehler T, Mayerle J, Quietzsch D, Reinacher-Schick A, Schenk M, Seipelt G, Siveke JT, Stahl M, Vehling-Kaiser U, Waldschmidt DT, Dorman K, Zhang D, Westphalen CB, von Bergwelt-Baildon M, Boeck S, Haas M. Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection? Clin Transl Oncol. 2024 May;26(5):1268-1272. doi: 10.1007/s12094-023-03323-1. Epub 2023 Oct 4.

  PMID: 37794220 DERIVED

• Guenther M, Surendran SA, Haas M, Heinemann V, von Bergwelt-Baildon M, Engel J, Werner J, Boeck S, Ormanns S. TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer. Br J Cancer. 2023 Jul;129(1):175-182. doi: 10.1038/s41416-023-02295-x. Epub 2023 May 4.

  PMID: 37142730 DERIVED

• 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.

  PMID: 32830200 DERIVED

• 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.

  PMID: 25164437 DERIVED

• 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.

  PMID: 22773551 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Capecitabine; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Volker Heinemann, MD

  University of Munich - Klinikum Grosshadern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Delegatated Person

Study Record Dates

• First Submitted: February 22, 2007
• First Posted: February 26, 2007
• Study Start: June 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: July 9, 2012

Record last verified: 2012-07