Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00000600

Trial Description

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Title

Multicenter Phase-II-Study with Capecitabine/Trastuzumab as first-line therapy for advanced HER2-overexpressing pancreas carcinoma

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Trial Acronym

ML17-743

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URL of the Trial

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Brief Summary in Lay Language

A therapy for advanced pancreas carcinoma by surgical removal which is the cure for early stages is not possible. Chemotherapy and radiation therapy had only small success rates.
During the last few years a few drugs have been whic had an effect in different malignant tumors.
The new substance capecitabine is converted into the effective drug in tumor tissue. The conversion into the effective drug at the location of the tumor helps to minimize toxicities and side effects concerning other organs. Capecitabine can be applied orally in tablet form. Therefore venous port systems and intravenou infusions are not necessary. A therapeutic response for Capecitabine has been observed for patients with pancreas carcinoma.
A second new medication Trastuzumab has a specific effect on tumor cells, which have a specific protein (HER2/neu) in large quantities on their surface. Trastuzumab is an antibody, which is directed against the target structure (HER2) and slows down tumor growth. Up to 30% of all pancreas carcinomas carry a sufficient amount of this target proptein. The presence of the target will be assessed by tissue biopsy festgestellt. The medication will be applied once a week by infusion.Preliminary studies for pancrea carcinoma with a combination of Trastuzumab and other Chemotherapies a response.
This study was designed to find outif the combination of capecitabin and Trastuzumab in comparison with established chemotherapies shows a better response i. e. improves survival time and quality of life.

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Brief Summary in Scientific Language

A generall accepted standard-chemotherapy for advanced pancreas carcinoma does not exist. Therapy of advanced, inoperable pancreas carzinoma is still of palliative character. Therefore it is the goal of any therapy to achieve an improvement of survival time with optimal quality of life.
The specific mechanism of capecitabine (Xeloda®) by accumulation and activation in tumor tissue and the Inhibition of HER2 receptor mediated tumor cell proliferation by Trastuzumab (Herceptin®) can improve the prognosis of HER2 positive pancreas carcinoma. Because of differentv mechanisms there are no overlapping toxicities. The side effects are all known, managable and reversible. The therapy can be applied on an outpatient basis and fullfills the needs of a patient for a minimum of stays in the hospital. Because of the pharmacocinetic similarities and the advantages of oral capecitabine versus continuous infusion of 5-FU it appears to be in the interest of improvement of palliative therapies for pancreas carcinoma patients to design combination protocols of Capecitabine with Trastuzumab. Clinical data for this combination are not yet available for the pancreas carcinoma.
In this multicenter phase-II-study the combinationen of Capecitabin/Trastuzumab should be assessed for efficacy and toxicity for the therapy of advanced , inoperable pancreas carcinoma.

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Organizational Data

  •   DRKS00000600
  •   2010/11/11
  •   2005/12/01
  •   yes
  •   Approved
  •   269/03, Ethik-Kommission der Albert-Ludwig-Universität Freiburg
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Secondary IDs

  •   UKF000577  (Register klinischer Studien des Universitätsklinikums Freiburg)
  •   4021536 
  •   ML 17 743 
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Health Condition or Problem studied

  •   C25.9 -  Malignant neoplasm: Pancreas, unspecified
  •   10033576
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Interventions/Observational Groups

  •   Trastuzumab 4 mg/kg as initial infusion, followed by 2 mg/kg weekly and Capecitabin 2 x 1250 mg/m2 daily for days 1-14 followed by 7 days pause; repeated every three weeks until tumour progression.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
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Primary Outcome

progression free survival rate after 12 weeks

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Secondary Outcome

progression free survival
- overall survival -
- time to remission (complete/partial)
- duration of remission
- Rate of "Clinical Benefit Response" after 12 weeks
- quality of life before therapy and after every second chemotherapy cycle
- Toxicity and occurrence of adverse events
- impact of CA19-9 serum concentration on progression free survival
- correlation between tumour HER2-expression grade and progression free survival

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2004/09/14
  •   37
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Written informed consent
- Age over 18
- Histological confirmed diagnoss of a pancreas carcinoma in Stage IVB (T1-4, N0-1, M1)
- Staging and CA 19-9 Determiantion not older than 4 weeks
- Histologically confirmed overexpression of HER2/neu (immunhistochemical Score 2+ (confirmed by FISH ) or 3+)
- At least one measurable or assessable lesion over 2 cm in conventional CT
- No previous chemotherapy
- No previous radiation therapy
- Performance-Status 0 - 2 WHO/ECOG or better 60 Karnofsky
- life expectancy at least 3 month
- Sufficient renal, hepatic and bonemarrow function,
(blood values not older than 1 weel) defined as
absolute Neutrophil count greater 1,5 x 10 exp9/l,
Hemoglobin greater 80 g/l, platelets greater 100 x 10exp 9 /l, total bilirubin smaller 3-fold upper normal value, creatinine clearance greater 30ml/min (according to Cockroft and Gault), Transaminases smaller 2,5-fold upper normal value, smaller 5-fold upper normal value in case of liver metastases.
- LVEF > 50%
- infrastructure for regular and longterm followup
- Negative pregnancy test for women in reproductive age (done during Screening)

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Exclusion Criteria

Option of surgical treatment or radiation therapy with curative intention
- Known Dihydropyrimidin dehydrogenase (DPD) deficiency
- History of known secondary carcinoma with exception of basalioma of skin treated in curative intention or cervical carcinoma in situ
- Known hypersensitivity to one of the study medications or their ingredients
- Clinical relevant disease of the cardiovascular system or other major organ systems or significant systemic disease, which is incompatible with the procol or complicates the interpretation of the protocol.
- Clinically signioficant pulmonary disease
- Preexisting polyneuropathy
- Simultaneous therapy with the virostatic agent Sorivudin or chemically related substances, for instance Brivudin
- Pragnancy, lactation or lack of reliable contraception for women in their reproductive age
- Psychiatric disease, addiction or other disease, which keep the patient from understanding character and consequences of the study
- Simultaneous participation in a different clinical study within the last 4 weeks
- Any disease or therapy, which presens a risk to the patient in the mind of the investigator or is not compatible with the goals of the study

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Addresses

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    • Universitätsklinikum Freiburg Abteilung Innere Medizin II - Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie
    • Mr.  Prof. Dr. med.  Michael  Geißler 
    • Hugstetterstr. 49
    • 79110  Freiburg
    • Germany
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    • Abteilung für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie Klinikum Esslingen GmbH
    • Mr.  Prof. Dr. med.  Michael  Geißler 
    • Hirschlandstr. 97
    • 73730  Esslingen
    • Germany
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    • Abteilung für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie
    • Mr.  Prof. Dr. med.  Michael  Geißler 
    • Hirschlandstr. 97
    • 73730  Esslingen
    • Germany
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Sources of Monetary or Material Support

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    • Hoffmann-La Roche AG
    • Emil-Barell-Straße 1
    • 79630  Grenzach-Wyhlen
    • Germany
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Status

  •   Recruiting stopped after recruiting started
  •   2008/05/01
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Trial Publications, Results and other Documents

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