Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer (CHERLOB)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00429299
First received: January 29, 2007
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Neoplasms, Breast
Drug: lapatinib
Biological: trastuzumab
Drug: paclitaxel
Drug: fluorouracil
Drug: epidoxorubicin
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemotherapy Plus Lapatinib or Trastuzumab or Both in Her2+ Primary Breast Cancer. A Randomized Phase IIb Study With Biomarker Evaluation.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Pathological complete responses (pCR) in the breast and in the lymph nodes Assessed after 24 weeks, prior to definitive surgery [ Time Frame: Approx. 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Approx. 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 121
Study Start Date: August 2006
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Chemotherapy plus trastuzumab
Biological: trastuzumab
First dose 4mg/kg in 60mins, then weekly 2mg/kg in 30 mins
Other Name: Herceptin
Drug: paclitaxel
80mg/sqm 1 hour infusion for 12 weeks
Other Name: Taxol
Drug: fluorouracil
600mg/sqm iv day 1 q21 days for four coursess
Drug: epidoxorubicin
75mg/sqm iv day 1 q21 days for four courses
Drug: cyclophosphamide
600mg/sqm day 1 q21 days for four courses
Experimental: Arm B
Chemotherapy plus lapatinib
Drug: lapatinib
Arm B 1250mg/d PO Arm C 750mg/d PO
Other Name: Tyverb/Tykerb
Drug: paclitaxel
80mg/sqm 1 hour infusion for 12 weeks
Other Name: Taxol
Drug: fluorouracil
600mg/sqm iv day 1 q21 days for four coursess
Drug: epidoxorubicin
75mg/sqm iv day 1 q21 days for four courses
Drug: cyclophosphamide
600mg/sqm day 1 q21 days for four courses
Active Comparator: Arm C
Chemotherapy plus trastuzumab plus lapatinib
Drug: lapatinib
Arm B 1250mg/d PO Arm C 750mg/d PO
Other Name: Tyverb/Tykerb
Biological: trastuzumab
First dose 4mg/kg in 60mins, then weekly 2mg/kg in 30 mins
Other Name: Herceptin
Drug: paclitaxel
80mg/sqm 1 hour infusion for 12 weeks
Other Name: Taxol
Drug: fluorouracil
600mg/sqm iv day 1 q21 days for four coursess
Drug: epidoxorubicin
75mg/sqm iv day 1 q21 days for four courses
Drug: cyclophosphamide
600mg/sqm day 1 q21 days for four courses

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429299

Locations
Germany
GSK Investigational Site
Berlin, Germany, 13125
Italy
GSK Investigational Site
Carpi (MO), Emilia-Romagna, Italy, 41012
GSK Investigational Site
Forlì, Emilia-Romagna, Italy, 47100
GSK Investigational Site
Modena, Emilia-Romagna, Italy, 41100
GSK Investigational Site
Parma, Emilia-Romagna, Italy, 43100
GSK Investigational Site
Piacenza, Emilia-Romagna, Italy, 29100
GSK Investigational Site
Rimini, Emilia-Romagna, Italy, 47900
GSK Investigational Site
Treviglio (BG), Lombardia, Italy, 24047
GSK Investigational Site
Candiolo (TO), Piemonte, Italy, 10060
GSK Investigational Site
Brindisi, Puglia, Italy, 72100
GSK Investigational Site
Pisa, Toscana, Italy, 56126
GSK Investigational Site
Cremona, Italy, 26100
GSK Investigational Site
Pavia, Italy, 27100
GSK Investigational Site
Perugia, Italy, 06156
GSK Investigational Site
Reggio Emilia, Italy, 42100
GSK Investigational Site
Varese, Italy, 21100
Poland
GSK Investigational Site
Warszawa, Poland, 00-909
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00429299     History of Changes
Other Study ID Numbers: EGF106988
Study First Received: January 29, 2007
Last Updated: July 26, 2012
Health Authority: Italy: Ministry of Health
Germany: Ministry of Health
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
neo-adjuvant trastuzumab early breast cancer lapatinib

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Trastuzumab
Lapatinib
Epirubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014