Evaluating Lapatinib + Capecitabine in Patients Aged 70 and Over With HER2 Metastatic Breast Cancer. (GERICO09)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01262469
First received: December 16, 2010
Last updated: September 2, 2013
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Metastatic Breast Cancer
70 Years Old Patients and Over
After One Line of Chemotherapy With Trastuzumab
Drug: lapatinib + capecitabine
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 52
Study Start Date: December 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Other Names:
  • Tyverb
  • Xeloda

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

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01262469

Locations
France
Centre Paul Papin
Angers, France, 49933
Centre Hospitalier de Beauvais
Beauvais, France, 60021
Clinique Tivoli
Bordeaux, France, 33000
Ch Fleyriat
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
Hegp-Hopital Broussais
Paris, France, 75015
Institut Curie
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
Sponsors and Collaborators
UNICANCER
GlaxoSmithKline
Investigators
Principal Investigator: Véronique GIRRE CHD Vendée
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01262469     History of Changes
Other Study ID Numbers: GERICO 09/0907, 2009-015981-73
Study First Received: December 16, 2010
Last Updated: September 2, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Fluorouracil
Lapatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014