Clinical trial NCT01262469: Evaluating Lapatinib + Capecitabine in Patients Aged 70 and Over With HER2 Metastatic Breast Cancer.
Official title: PHASE II STUDY Evaluating the Toxicity and Activity of the Combination Lapatinib + Capecitabine in Elderly Patients Aged 70 and Over With Metastatic Breast Cancer Over Expressing HER2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
70 Years Old Patients and Over
After One Line of Chemotherapy With Trastuzumab
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-12-17
Enrollment: 4
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: GERICO 09/0907 is a Phase II multicentric trial evaluating the toxicity and activity of the combination of lapatinib and capecitabine in locally advanced or metastatic breast cancer over expressing HER2 for patients aged ≥ 70 who have failed after one line of chemotherapy in combination with trastuzumab.

Due to the minimal participation of older people in clinical trials, there is a lack of data to make evidence-based decisions regarding chemotherapy in this indication.

The study is designed to investigate whether elderly patients with locally advanced or metastatic breast cancer over-expressing HER2 could take advantage of the combination lapatinib and capecitabine in term of clinical benefit, and with no adverse effects and no detrimental impact on functional status (part of geriatric assessment).

The main objective is to assess clinical benefit (defined at 4 months as complete response, partial response or stable disease), safety and preserved geriatric independence (main objective is a "bi-criteria" or composite criteria).

Detailed description: More than half of patients who have breast cancer with Her2-positive tumors treated with trastuzumab as a single agent develop resistance within one year of treatment initiation.

Recent studies on this population of patients show that the use of Capecitabine combined with Lapatinib demonstrates an improvement of TTP without an increase of serious toxic effects.

Our study is designed to investigate whether elderly patients with locally advanced or metastatic breast cancer over-expressing HER2 could take advantage of the combination lapatinib (1250mg/day) and capecitabine (1st cycle day 1 to day 14: 850mg/m2/day x2; next cycles day 1 to day 14: 1000 mg/m2/day x2) in term of clinical benefit, and with no adverse effects and no detrimental impact on functional status (part of geriatric assessment). Treatment will continue until disease progression or unacceptable toxicity occurence.

This is a phase II multicentric trial associated to a pharmacokinetic study which aims to assess the effect of age modifications (absorption, distribution, metabolism and elimination) on the combination Lapatinib-Capecitabine by measuring the Cmin-Cmax of both components in elderly patients.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 70
* Histological confirmed advanced breast cancer (metastatic or locally advanced)
* Tumor over expressing HER2 (HER2 3+ in IHC or IHC 2+ and Fish positive) in sample from the primary and/or secondary tumor
* WHO performance status (EGOG) from 0 to 2
* MMS \> 25
* Measurable disease (RECIST criteria)
* Progression of disease after one metastatic line of chemotherapy associated with trastuzumab (must be stopped at least 3 weeks before beginning the trial)
* Adequate hematological function (Hb ≥ 10g/dl, ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3)
* Adequate hepatic function (total bilirubine ≤ 1.5ULN, ASAT and ALAT ≤ 3ULN)
* Adequate renal function (measured or calculated creatinine clearance ≥ 40 ml/min - Cockroft)
* LVEF ≥ 50% (US or isotopic method)
* Absence of treatment by enzymatic inhibitors or inducers or any gastric pH modifying agent/drug within a 7-to-14 day period preceding the first administration of one of the trial's products and within the overall duration of the study (see medication list)
* Patients must be affiliated to a Social Security System
* Patient information and written informed consent form signed

Exclusion Criteria:

* Life expectancy \< 3 months
* Prior treatment with capecitabine or lapatinib
* Concomitant radiotherapy except for palliative reason and more than 25% of the BM
* Patients with pre-existing toxicity ≥ grade 2 (excepted alopecia)
* Patients with dysphagia, or inability to swallow the capsules.
* Patient with malabsorption syndrome or disease significantly affecting gastro-intestinal function or with major resection of stomach or proximal bowel that could affect absorption of oral drugs
* Patient already included in another therapeutic trial using an experimental drug within 30 days preceding entry into the study
* Individual deprived of liberty or placed under the authority of a tutor
* Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Primary outcomes:
measure: Efficacy assessment
timeFrame: at 4 months
measure: Tolerance criteria and impact on functional status
timeFrame: at 4 months
Secondary outcomes:
measure: Duration of clinical benefit
timeFrame: from treatment start until disease progression
measure: Time to progression
timeFrame: from inclusion to disease progression or death due to breast cancer
measure: Overall response rate
timeFrame: from treatment start until end of treatment
measure: Progression free survival
timeFrame: from inclusion to disease progression or death due to any cause
measure: Overall survival
timeFrame: from inclusion until death due to any cause or last follow-up news (censored data)
measure: Time to treatment failure endpoint
timeFrame: from inclusion to end of treatment
measure: Determination of toxicity of the combination (NCI-CTC vers.4)
timeFrame: from informed consent signature to one month after last study drug intake
measure: Geriatric Evaluation
timeFrame: At baseline, at uneven cycles, at end of treatment and at follow-up visits (every 6 months)
measure: Determination of the minimal and maximal concentration of lapatinib and capecitabine
timeFrame: at Day1 Cycle1 and Day1 Cycle3
measure: Number of patients treated with 3 and 6 cycles and % of dose administrated
timeFrame: From treatment start until 6 cycles of treament
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Beauvais
country: France
facility: Centre Hospitalier de Beauvais
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Bourg-en-Bresse
country: France
facility: Ch Fleyriat
city: Brest
country: France
facility: Institut Cancérologie- CENTRE HOSPITALIER BREST
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lagny-sur-Marne
country: France
facility: Centre Hospitalier de Lagny-Sur-Marne
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Centre Rene Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: Centre Hospitalier Orleans La Source
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hegp-Hopital Broussais
city: Reims
country: France
facility: Polyclinique de Courlancy
city: Roanne
country: France
facility: Centre Hospitalier de Roanne
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Centre Rene Huguenin
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: CHD Vendée
name: Véronique GIRRE
role: PRINCIPAL_INVESTIGATOR
References: