Adjunction with Capecitabin, Lapatinib and Vinorelbin to treat patients with HER2/new-positive, advanced or metastized breast cancer after failure of Trastuzumab

• Conditions: Female patients with HER2/new-positive, locally advanced or metastized breast cancer after failure of chemotherapy with Trastuzumab; MedDRA version: 15.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-017219-13-DE
• Lead Sponsor: Deutsche Krebsgesellschaft Sponsor GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-19
• Last Update Posted: 18 September 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

General
1. written informed consent
2. patient age = 18 years
3. willingness and ability to comply with study protocol
4. secured contraception for sexual active females with childbearing potential respectively secured postmenopausal state (at least two years of amenorrhea or confirmed by hormonal state). The contraception must be continued for 6 months after the end of treatment.

Tumor
5. histologically secured adenocarcinoma in breast (unilateral or bilateral)
6. Status: locally advanced or metastized
7. HER2/new-Status positive (3+ ICH or FISH/CISH positive)
8. at least one measurable lesion according to RECIST 1.1 criteria
9. first or second chemotherapy after diagnosis of metastasis
10. existing indication for therapy with Lapatinib, i.e.
2nd line after Trastuzumab-therapy or
1st line if adjuvant Trastuzumab-therapy < 12 months ago
Anthracycline- and Taxan-therapy in adjuvant/palliative indication is not obligatory

State of health
11. good general state of health (ECOG Performance Status 0-1), symptomatic regarding tumor disease
12. no congestive heart insufficiency symptoms, respectively no suspicion of congestive heart insufficiency, LVEF at timepoint of enrolment at least55%
13. adequate liver and renal function, defined as:
- albumin > 2,5 g/dl,
- serous bilirubin = 2 mg/dl or up to triple upper normal value under liver metastasis
- AST and ALT up to 2,5-fold upper normal value, respectively fivefold upper normal value under documented liver metastasis
- serous creatinine in normal range or creatinin-clearance > 60 ml/min (according to Cockroft/Gault formula) if serous creatinine is out of range
14. adequate hematopoietic Funktion:
- neutrophile granulocytes > 1500/ µl
- haemoglobin > 10g/dl
- thrombocytes > 100 000/ µl

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

General
1. pregnant or breastfeeding females. Urine or serum pregnancy test prior to treatment start is indicated for all females with childbearing potential.
2. synchronous participation in another clinical study, synchronous treatment with a product without marketing authorization. The participation in a former clinical study does not conflict with a registration as long as the last medication with another study drug was more than four weeks ago.
3. asymptomatic regarding tumor disease.

Permitted former or ongoing antineoplastic therapies
4. former treatment with Lapatinib, Capecitabin or Vinorelbin
5. essential or intended treatment with other cytostatic drugs or anti-hormone therapy.

Pre-existing conditions
6. significant injury, major surgical interventions or open biopsies during the past 28 days prior to enrolment or during the study period, not completely healed traumata after surgery
7. indication for cardiovascular diseases in 2-D echocardiograph or electrocardiogram, particularly myocardial insufficiency, unstable angina pactoris or arrhythmia
8. relevant vascular diseases or cardiovascular system diseases (e.g. arterial or venous thrombosis, myocardial infarct, ischaemic seizure, angioplstica or stents or cerebrovaskular events) during the past six months
9. every disease, which might have an influence on resorption or kinetics, i.a.: Malabsorption syndrome, significant influence on gastrointestinal function or not minimal surgical interventions in gastrointestinal tract, colitis ulcerosa, ileus etc.
10. synchronous treatment with virostatic drugs of Sorivudin-type or aminoglycoside
11. concomitant medication with products inducing CYP3A (e.g. Rifabutin, Rifampicin, Clarithromycin, Ketoconazol, Itroconazol, Ritinavir, Telithromycin, Erythromycin, Verapamil, Diltiazem, etc.)
12. concomitent medication with Allopurinol (interaction with Capecitabin)
13. other malignant tumour (beside basal cell carcinoma and cervical carcinoma in situ) in medical history. The patient can be enrolled regardless being in complete remission for 5 years.
14. concomitant diseases or other circumstances e.g. in family or psychologic, that might have an influence on patient's ability to participate, the efficacy of the products or patients safety.

Contraindication against products of antineoplastic combination therapy
15. known dihydropyrimidine dehydrogenase deficiency or former serious reaction under fluoropyrimidine administration (with or withot established dihydropyrimidine dehydrogenase deficiency)
16. anaphylaxis or allergy against one of the agents or the excipients contained in the product.
17. allergy against CHO-cell products or other human antibodies
18. known anaphylaxis of acute type or delayed type against agants chemically related with Capecitabin, Vinorelbin or Lapatinib.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase I:<br>Identification of maximal tolerable dose (MTD) of Vinorelbin as combination therapy with Lapatinib and Capecitabin <br><br>Phase II:<br>Remission rate of the combination CLV under maximal tolerable dose (MTD)<br><br>;Secondary Objective: Progression Free Survival (PFS), Time To Treatment Failure (TTF) und occurence of (particularly cardiovascular) toxicities, Overall Survival (OS);Primary end point(s): Phase I:<br>Identification of maximal tolerable dose (MTD) during the first chemotherapy cycle. MTD is defined as the highest dose level, at which 1/3 of the patients experience a dose limiting toxicity (DLT)<br><br>Phase II:<br>Determination of overall response rate (ORR=complete response+partial response) of the combination therapy CLV under maximal tolerable dose (MTD)