Dose Finding Study for Combination of Capecitabine, Lapatinib and Vinorelbine in Metastatic Breast Cancer (CELAVIE)

Combinational Therapy of Capecitabine, Lapatinib and Vinorelbine for the Treatment of Patients With her2/Neu Positive, Relapsed or Metastatic Breast Carcinoma Following Treatment Failure With Trastuzumab

The purpose of the study is to investigate safety and efficiency of the triple combination of capecitabine, lapatinib and vinorelbine in patients with metastatic breast cancer.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer; HER2 Positive; First or Second Line Therapy; Failure or Contraindication of Trastuzumab Therapy
• Intervention / Treatment: Drug: Lapatinib and Capecitabine and Vinorelbine

Detailed Description

The combination of lapatinib with capecitabine ist a standard therapy für Her2 positive metastatic breast cancer. This study combines this therapy with the additional antimitotic mode of function by vinorelbine.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69115
    • Onkologische Schwerpunktpraxis
  • Baden-Württemberg
    • Ravensburg, Baden-Württemberg, Germany, 88214
      • Onkologie Ravensburg
  • Hessen
    • Kassel, Hessen, Germany, 34117
      • Praxisgemeinschaft Dres. Siehl und Söling
  • Niedersachsen
    • Goslar, Niedersachsen, Germany, 38642
      • Onkologische Schwerpunktpraxis
    • Leer, Niedersachsen, Germany, 26789
      • Onkologische Schwerpunktpraxis Leer Emden
    • Stade, Niedersachsen, Germany, 21680
      • Schwerpunktpraxis Hämatologie / Onkologie
  • Nordrhein-Westfalen
    • Guetersloh, Nordrhein-Westfalen, Germany, 33332
      • Onkodok (Dr. Rösel und Dr. Depenbusch)
    • Mulheim an der Ruhr, Nordrhein-Westfalen, Germany, 45468
      • Praxis fur Hamatologie und Onkologie
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Hämatologisch-onkologische Gemeinschaftspraxis
    • Neuss, Nordrhein-Westfalen, Germany, 41462
      • Praxis für Onkologie u. Hämatologie
  • Saxony
    • Dresden, Saxony, Germany, 01127
      • Onkologische Gemeinschaftspraxis Dörfel/Göhler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key Inclusion Criteria:

• Written informed consent
• Able to comply with the protocol
• ECOG performance status 0-1
• Adequate contraception
• Confirmed Her2/neu-positive, adenocarcinoma of the breast
• At least one measurable lesion according to RECIST 1.1 criteria
• First or second chemotherapy after diagnosis of metastasis
• Lapatinib treatment indicated (adjuvant trastuzumab treatment <12 months ago or progressive disease with trastuzumab treatment)
• No signs and symptoms of CHF (chronic heart failure), LVEF (left ventricular ejection fraction) at study start at least 55%
• Adequate hepatic and renal function value
• Adequate hematologic function values

Exclusion Criteria:

• Pregnant or lactating women
• Concurrent participation in another clinical trial. Prior participation is allowed if the last study medication was administered more than 4 weeks prior to randomization
• Asymptomatic with regards to tumor illness
• Previous treatment with lapatinib, capecitabine or vinorelbine
• Necessity of planned treatment with other chemotherapeutics oder anti-hormone therapy
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study
• Evidence of cardiovascular disease, e.g. myocardial infection, unstable angina pectoris or arrhythmia
• History of vascular or cardiovascular disease within the past 6 months
• All illnesses that result in malabsorption of oral medication or inability to take oral medication
• Concurrent treatment with anti-viral drugs based on sorivudine or with aminoglycosides
• Concurrent treatment with any drug interfering with study medication, especially, those that induce CYP3A
• Concurrent treatment with allopurinol
• Other malignancies (except for basal cell carcinoma of the skin and cervical carcinoma in situ); patient can be included in the study if no recurrent disease has been observed for at least 5 years
• Concurrent illnesses or other circumstances that could interfere with trial participation, efficacy or safety of the patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capecitabine, Lapatinib, Vinorelbine	Drug: Lapatinib and Capecitabine and Vinorelbine; Dose finding Study Lapatinib: 1000-1250 oral, once daily, days 1-21 Capecitabine: 1000 mg/sqm oral, bid, days 1-14 Vinorelbine 10-22,5 mg/sqm, i.v. Day 1 + 8; Other Names: Xeloda; Tyverb; Navirel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of maximal tolerable Dose (MTD) of combination with Capecitabine and Lapatinib and Vinorelbine	Phase I: Identification of Dosis limiting toxicities and maximal tolerable dose for Combinational therapy (Time Frame: within the first 21 days under medication)	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response Rate	Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected.	12 months
Progression free survival	Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected.	12 months
Time to treatment failure (TTF)	Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected.	12 months
Overall survival (OS)	Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected.	12 months

Collaborators and Investigators

• Sponsor: Sponsor GmbH
• Collaborators: GlaxoSmithKline; iOMEDICO AG; Arbeitsgemeinschaft fur Internistische Onkologie; Arbeitskreis Klinische Studien
• Investigators: Principal Investigator: Ulrike Soeling, MD, Goethestr. 47, 34119 , Kassel, Germany

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 2, 2010
• First Submitted That Met QC Criteria: November 9, 2010
• First Posted (Estimate): November 10, 2010

Study Record Updates

• Last Update Posted (Estimate): November 21, 2014
• Last Update Submitted That Met QC Criteria: November 20, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Combination; Dose finding study
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Capecitabine; Vinorelbine; Lapatinib
• Other Study ID Numbers: 0907-002