Evaluating Lapatinib + Capecitabine in Patients Aged 70 and Over With HER2 Metastatic Breast Cancer. (GERICO09)
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).
Metastatic Breast Cancer
70 Years Old Patients and Over
After One Line of Chemotherapy With Trastuzumab
Drug: lapatinib + capecitabine
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Efficacy assessment [ Time Frame: at 4 months ] [ Designated as safety issue: Yes ]
Benefit is defined as complete response, partial response, or stable disease according to RECIST criteria (vers. 1.1).
Efficacy criteria is the number of patients meeting this definition. Patients having stopped before this 4-months time point will be considered as non responders without clinical benefit.
- Tolerance criteria and impact on functional status [ Time Frame: at 4 months ] [ Designated as safety issue: Yes ]The criteria is the number of patients for whom a toxicity event (according to the NCI-CTC AE vers.4)and/or an impact on functional status (defined by the 8 items IADL assessment scale) has been observed during the first 4 months of treatment.
- Duration of clinical benefit [ Time Frame: from treatment start until disease progression ] [ Designated as safety issue: Yes ]
- Time to progression [ Time Frame: from inclusion to disease progression or death due to breast cancer ] [ Designated as safety issue: Yes ]
- Overall response rate [ Time Frame: from treatment start until end of treatment ] [ Designated as safety issue: Yes ]
- Progression free survival [ Time Frame: from inclusion to disease progression or death due to any cause ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: from inclusion until death due to any cause or last follow-up news (censored data) ] [ Designated as safety issue: Yes ]
- Time to treatment failure endpoint [ Time Frame: from inclusion to end of treatment ] [ Designated as safety issue: Yes ]Treatment stop can be due to toxicity, death, refusal to continue study, or progressive disease.
- Determination of toxicity of the combination (NCI-CTC vers.4) [ Time Frame: from informed consent signature to one month after last study drug intake ] [ Designated as safety issue: Yes ]
- Geriatric Evaluation [ Time Frame: At baseline, at uneven cycles, at end of treatment and at follow-up visits (every 6 months) ] [ Designated as safety issue: No ]Activities of daily Living (ADL)/ Instrumental ADL(IADL), Geriatric depression scale (GDS), Mini Mental States (MMS), comorbidities (CIRGS), G8 (oncodage), Vulnerable Elders Survey (VES13), QLQC30 item 29-30.
- Determination of the minimal and maximal concentration of lapatinib and capecitabine [ Time Frame: at Day1 Cycle1 and Day1 Cycle3 ] [ Designated as safety issue: No ]
The samples time points are the followings:
T0 : before administration of treatment (lapatinib is administered 1 hour before meal and capecitabine 30 min before meal)
T1 : time for Cmax (2 hrs post-dose lapatinib and 90 min post-dose of capecitabine)
- Number of patients treated with 3 and 6 cycles and % of dose administrated [ Time Frame: From treatment start until 6 cycles of treament ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Lapatinib + Capecitabine
lapatinib 1250 mg/day (once daily) Capecitabine 2x850 mg/m2/day, days 1-14 during the first cycle and 2x1000 mg/m2/day, days 1-14, every 21 days for following cycles ( if no unacceptable toxicity is observed).
Drug: lapatinib + capecitabine
For Lapatinib: 5 tablets of 250 mg each, once daily, until disease progression or unacceptable toxicity occurence.
For Capecitabine: 850 mg/m2 twice a day from day 1 to 14 of cycle 1 and 1000 mg/m2 twice a day from day 1 to 14 of the next cycles.
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.
|Centre Paul Papin|
|Angers, France, 49933|
|Centre Hospitalier de Beauvais|
|Beauvais, France, 60021|
|Bordeaux, France, 33000|
|Bourg-en-Bresse, France, 01012|
|Institut Cancérologie- CENTRE HOSPITALIER BREST|
|Brest, France, 29200|
|Centre Francois Baclesse|
|Caen, France, 14076|
|Centre Hospitalier de Lagny-Sur-Marne|
|Lagny-sur-Marne, France, 77405|
|Centre Oscar Lambret|
|Lille, France, 59020|
|Institut Paoli Calmettes|
|Marseille, France, 13273|
|Centre Rene Gauducheau|
|Nantes, France, 44805|
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Centre Hospitalier Orleans La Source|
|Orléans, France, 45100|
|Paris, France, 75015|
|Paris, France, 75005|
|Polyclinique de Courlancy|
|Reims, France, 51100|
|Centre Hospitalier de Roanne|
|Roanne, France, 42328|
|Centre Henri Becquerel|
|Rouen, France, 76038|
|Centre Rene Huguenin|
|Saint-Cloud, France, 92210|
|Centre Paul Strauss|
|Strasbourg, France, 67065|
|Institut Claudius Regaud|
|Toulouse, France, 31052|
|Principal Investigator:||Véronique GIRRE||CHD Vendée|