Last updated: 11/04/2018 06:29:29
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast CancerCHERLOB
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: Chemotherapy plus lapatinib or trastuzumab or both in Her2+ primary breast cancer. A randomized phase IIb study with biomarker evaluation.
Trial description: Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with chemotherapy in the preoperative (neoadjuvant) treatment of early breast cancer.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Percentage of participants with pathological complete response (pCR) in the breast and in the lymph nodes
Timeframe: At Baseline and surgery (within 5 weeks after the last chemotherapy administration) (assessed up to Study Week 29)
Secondary outcomes:
Percentage of participants with the indicated clinical objective response (complete response and partial response), stable disease, and progressive disease, as assessed by ultrasonography
Timeframe: At Baseline and after primary treatment (within 2 weeks before surgery; up to Study Week 27)
Percentage of participants who had breast-conserving surgery (BCS), mastectomy, and conversion from mastectomy to BCS
Timeframe: At Baseline and at surgery (up to Study Week 29)
Time to treatment failure from the start of primary therapy
Timeframe: From randomization up to Study Week 307
Number of participants with treatment failure
Timeframe: From randomization up to 29 weeks
Percentage of inhibition of biomarkers Ki67, pAKT, pMAPK, Tunel test, PTEN, and pEGFR after treatment
Timeframe: At Baseline and Withdrawal (assessed up to Study Week 29)
Number of participants with any adverse event (AE), including serious adverse events (SAEs), occurring in >=5% of participants
Timeframe: From the first dose of randomized therapy to 30 days after the last dose of randomized therapy (assessed up to Study Week 29)
Number of variations/somatic mutation in PI3KCA at Baseline
Timeframe: Baseline
Interventions:
Drug: lapatinib
Biological/vaccine: trastuzumab
Drug: paclitaxel
Drug: fluorouracil
Drug: epidoxorubicin
Drug: cyclophosphamide
Enrollment:
121
Observational study model:
Not applicable
Primary completion date:
2012-30-06
Time perspective:
Not applicable
Clinical publications:
Conte et al. Preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2 positive operable breast cancer: results of the randomized phase II CHER-LOB study.. [J Clin Oncol]. 2012;
Medical condition
Neoplasms, Breast
Product
lapatinib
Collaborators
Not applicable
Study date(s)
August 2006 to June 2012
Type
Interventional
Phase
2
Participation criteria
Sex
Female
Age
18 - 65 years
Accepts healthy volunteers
No
- Histologically confirmed infiltrating primary breast cancer of > 2.0 cm in largest clinical diameter
- HER2 positive tumor (either IHC 3+ or FISH+)
- Stage IIIB, IIIC, and inflammatory breast cancer
- Stage IV breast cancer
Inclusion and exclusion 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
Trial location(s)
Location
GSK Investigational Site
Candiolo (TO), Piemonte, Italy, 10060
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Carpi (MO), Emilia-Romagna, Italy, 41012
Status
Study Complete
Location
GSK Investigational Site
Piacenza, Emilia-Romagna, Italy, 29100
Status
Study Complete
Location
GSK Investigational Site
Treviglio (BG), Lombardia, Italy, 24047
Status
Terminated/Withdrawn
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
No longer a GSK study
Actual primary completion date
2012-30-06
Actual study completion date
2012-30-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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