Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer

Neoplasms, Breast Clinical Trial

— CHERLOB  

Official title:

Chemotherapy Plus Lapatinib or Trastuzumab or Both in Her2+ Primary Breast Cancer. A Randomized Phase IIb Study With Biomarker Evaluation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00429299
• Other study ID #: EGF106988
• Status: Completed
• Phase: Phase 2
• First received: January 29, 2007
• Last updated: July 26, 2012
• Start date: August 2006
• Est. completion date: June 2011

Study information

• Verified date: July 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of HealthGermany: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with chemotherapy in the preoperative (neoadjuvant) treatment of early breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

• Histologically confirmed infiltrating primary breast cancer of > 2.0 cm in largest clinical diameter

HER2 positive tumor (either IHC 3+ or FISH+)

• Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment

• Age >18, < 65 years

• ECOG PS 0-1

• Normal organ and marrow function as defined below:

leukocytes ³ 3000/microL

absolute neutrophil count ³ 1,500/microL

platelets ³ 100,000/microL

total bilirubin <= 1.5x ULN. In case of Gilbert's syndrome, <2 x ULN is allowed

AST (SGOT)/ALT(SGPT)<= 2.5 X institutional upper limit of normal

Alkaline phosphatase <= 2.5 x ULN

Creatinine within normal institutional limits

• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan

• Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided

• The effects of lapatinib on the developing human fetus at the recommended therapeutic dose are unknown; women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately, the patient should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy

• Ability to understand and the willingness to sign a written informed consent document

• Ability to swallow and retain oral medication

Exclusion criteria:

• Stage IIIB, IIIC, and inflammatory breast cancer

• Stage IV breast cancer

• Contraindication to the treatment with anthracycline, paclitaxel and/or trastuzumab

• Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with EGFR targeting therapies

• Treatment with any other investigational agents, or with all herbal (alternative) medicines

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib

• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnancy or breastfeeding; (breast feeding should be discontinued to be enrolled in the study)

• Women of childbearing potential that refusal to adopt adequate contraceptive measures

• HIV-positive patients receiving combination anti-retroviral therapy

• GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

• Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms, Breast

Intervention

Drug:
• lapatinib
Arm B 1250mg/d PO Arm C 750mg/d PO

Biological:
• trastuzumab
First dose 4mg/kg in 60mins, then weekly 2mg/kg in 30 mins

Drug:
• paclitaxel
80mg/sqm 1 hour infusion for 12 weeks
• fluorouracil
600mg/sqm iv day 1 q21 days for four coursess
• epidoxorubicin
75mg/sqm iv day 1 q21 days for four courses
• cyclophosphamide
600mg/sqm day 1 q21 days for four courses

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
Italy	GSK Investigational Site	Brindisi	Puglia
Italy	GSK Investigational Site	Candiolo (TO)	Piemonte
Italy	GSK Investigational Site	Carpi (MO)	Emilia-Romagna
Italy	GSK Investigational Site	Cremona
Italy	GSK Investigational Site	Forlì	Emilia-Romagna
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Italy	GSK Investigational Site	Parma	Emilia-Romagna
Italy	GSK Investigational Site	Pavia
Italy	GSK Investigational Site	Perugia
Italy	GSK Investigational Site	Piacenza	Emilia-Romagna
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Reggio Emilia
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Italy	GSK Investigational Site	Treviglio (BG)	Lombardia
Italy	GSK Investigational Site	Varese
Poland	GSK Investigational Site	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete responses (pCR) in the breast and in the lymph nodes Assessed after 24 weeks, prior to definitive surgery		Approx. 24 weeks	No
Secondary	Clinical objective responses (cOR) Incidence of conservative surgery Adverse events correlation between tumour gene expression at diagnosis and pathological response Assessed after 24 weeks, prior to definitive surgery		Approx. 24 weeks	No