Last updated: 11/04/2018 06:27:11
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 GSK Clinical Study Register is no longer maintained for this study.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.
Tykerb Evaluation After Chemotherapy (TEACH): Lapatinib Versus Placebo In Women with Early-Stage Breast Cancer
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib (GW572016) in Women with Early-Stage ErbB2 Overexpressing Breast Cancer
Trial description: This study was designed to evaluate and compare the safety and efficacy of an oral dual tyrosine kinase inhibitor, lapatinib, versus placebo in women with early-stage ErbB2-overexpressing breast cancer who have completed their primary neoadjuvant or adjuvant chemotherapy and have no clinical or radiographic evidence of disease.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants (par.) with any recurrence of the initial disease, second primary cancer, contralateral breast cancer, or death (disease-free survival [DFS])
Timeframe: From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])
Secondary outcomes:
Number of participants who died (overall survival)
Timeframe: From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])
Percentage of participants with the indicated period of recurrence-free survival (time to first recurrence)
Timeframe: From the date of randomization until the date of the first occurrence of an objective disease recurrence or contralateral breast cancer (assessed up to 6 years; 1 year of treatment and 5.3 years of follow-up [median of 5 years for final analysis])
Percentage of participants with the indicated period of distant recurrence-free survival (time to distant recurrence)
Timeframe: From the date of randomization until the date of the first occurrence of a distant recurrence (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])
Time to central nervous system (CNS) recurrence
Timeframe: From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])
Number of participants with CNS recurrence
Timeframe: From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])
Modified disease-free survival (MDFS)
Timeframe: From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)
Number of participants with any recurrence of the initial disease, contralateral breast cancer, or death (disease-free survival [DFS])
Timeframe: From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)
Change from Baseline in Short Form-36 version 2 (SF-36 v2) scores for the physical component summary (PCS)
Timeframe: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)
Change from Baseline in SF-36 v2 scores for the mental component summary (MCS)
Timeframe: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)
Change from Baseline in the SF-36 v2 domain scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)
Timeframe: Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)
Number of participants with hematology values outside the reference range for the indicated parameters
Timeframe: At Baseline and every 3 months thereafter up to Month 12/Early Withdrawal Visit
Number of participants with clinical chemistry values outside the reference range for the indicated parameters
Timeframe: At Baseline and every 6 weeks thereafter up to Month 12/Early Withdrawal Visit
Number of participants with non-laboratory toxicities of the indicated toxicity grades
Timeframe: From the first dose of study treatment up to 12 months
Number of participants experiencing primary or secondary cardiac events
Timeframe: From the date of randomization up to 12 months
Number of participants with the indicated electrocardiogram (ECG) findings
Timeframe: Screening and Month 12/Early Withdrawal Visit
Interventions:
Enrollment:
3166
Primary completion date:
2011-21-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
P Goss, I Smith, J O’Shaughnessy, B Ejlertsen, M Kaufmann, F Boyle, A Buzdar, P Fumoleau, W Gradishar, M Martin, B Moy, M Piccart-Gebhart, K I Pritchard, D Lindquist, Y Chavarri-Guerra, G Aktan, E Rappold, L S Williams, D M Finkelstein. Resubmission: A Randomized Trial of Adjuvant Lapatinib in Women with Early Stage HER2 Overexpressing Breast Cancer. Lancet Oncol. 2012;S 1470-2045(12):70508-9.
FM Boyle, IE Smith, J O’Shaughnessy, B Ejlertsen, M Kaufmann, AU Buzdar, P Fumoleau, W Gradishar, M Martin, B Moy, M Piccart-Gebhart, KI Pritchard, D Lindquist, M Amonkar, Y Huang, E Rappold, LS Williams, J Wang-Silvanto, T Kaneko, DM Finkelstein, PE Goss.Health Related Quality of Life of women in TEACH, a randomized placebo controlled adjuvant trial of lapatinib in Early Stage Human Epidermal Growth Factor Receptor (HER2) Overexpressing Breast Cancer .Eur J Cancer.2015;Epub ahead of print
P Goss, I Smith, J O’Shaughnessy, B Ejlertsen, M Kaufmann, F Boyle, A Buzdar, P Fumoleau, W Gradishar, M Martin, B Moy, M Piccart-Gebhart, K I Pritchard, D Lindquist, Y Chavarri-Guerra, G Aktan, E Rappold, L S Williams, D M Finkelstein.Resubmission: A Randomized Trial of Adjuvant Lapatinib in Women with Early Stage HER2 Overexpressing Breast Cancer.Lancet Oncol.2013;14(1):88-96
Medical condition
Neoplasms, Breast
Product
lapatinib
Collaborators
Not applicable
Study date(s)
August 2006 to July 2013
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
18+ years
Accepts healthy volunteers
No
- Have histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have undergone adequate excision of tumor;
- Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification by FISH (ErbB2 expression/amplification must be documented prior to study entry; however, a tumor tissue sample must be sent to a central laboratory for subsequent re-analysis of ErbB2 status);
- Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry;
- Had metachronous invasive breast cancer (breast cancers diagnosed at different times);
Inclusion and exclusion criteria
Inclusion criteria:
- Have histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have undergone adequate excision of tumor;
- Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification by FISH (ErbB2 expression/amplification must be documented prior to study entry; however, a tumor tissue sample must be sent to a central laboratory for subsequent re-analysis of ErbB2 status);
- Have Stage I through Stage IIIc disease according to the American Joint Committee on Cancer (6th edition) staging criteria for breast cancer and meet one of the following criteria: node-positive disease defined as: one positive lymph node by sentinel node biopsy OR at least 1 positive lymph node found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN1 or cN2 (if sentinel node biopsy is positive, subject may either undergo an axillary node dissection or radiotherapy to the axilla). node-positive disease evaluated as: ipsilateral axillary lymph nodes cN0-2 by clinical evaluation and axillary lymph nodes pNX, pN0(i+), or pN1-3 by pathological evaluation [patients with pN3 (Stage IIIc disease) must be disease free following completion of neoadjuvant or adjuvant chemotherapy for at least 12 months and must not have been lost to follow up]. OR node-negative disease defined as: negative sentinel node biopsy OR no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN0. node-negative disease categorized as: high-risk disease (tumor >2.0 cm if ER and/or progesterone receptor (PgR) positive disease is present or tumor >1.0 cm if ER and PgR negative disease) OR intermediate-risk disease (tumor 1.0-2.0 cm and ER and/or PgR positive disease).
- Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either the contralateral or ipsilateral breast at the time of the initial diagnosis are also eligible;
- Have undergone either mastectomy OR lumpectomy;
- Have received and completed treatment with a neoadjuvant or adjuvant chemotherapy regimen containing either an anthracycline or a taxane; or any cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen;
- May continue to receive endocrine therapy while taking study medication, if endocrine therapy was initiated as either adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer or for ovarian function suppression; however, endocrine therapy may not be initiated while taking study medication. Endocrine therapy agents may be switched while participating in this study (e.g., stop tamoxifen and start letrozole);
- May have received prior radiotherapy as treatment for primary tumor; however, is not required for study entry;
- May continue to receive radiotherapy while taking study medication, if radiotherapy was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer;
- May continue to receive bisphosphonates only for treatment of documented osteoporosis, but not as treatment or prophylaxis of bone metastases;
- All women eligible for adjuvant treatment with trastuzumab, including those diagnosed and treated within the last six months, must be considered for such treatment prior to being offered participation in this study. Participation in this study will be allowed only if the physician and patient have considered and discussed at length the advantages of trastuzumab, but have mutually decided against initiating trastuzumab therapy.
- Have clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry;
- if signs or symptoms suggestive of either recurrence of disease or metastatic disease are present, the appropriate radiological imaging must be performed
- if the following laboratory results are present, the appropriate radiological imaging must be performed:
- for AST/ALT ≥2×ULN or ALP ≥2×ULN (not in the bone fraction), an abdominal CT or MRI must be done
- for ALP≥2×ULN in the bone fraction, a bone scan must be done; a confirmatory x-ray, CT scan or MRI scan or biopsy is required if the results of the bone scan are inconclusive
- Have a unilateral/bilateral mammogram within 12 months prior to study entry;
- Have an analysis of both ER and PgR on the primary tumor prior to study entry;
- Have a cardiac ejection fraction within institutional range of normal as measured by either echocardiogram or multigated acquisition scans;
- Have an Eastern Cooperative Oncology Group Performance Status of 0 to 1;
- Women with a history of non-breast malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Women with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin;
- Are able to swallow and retain oral medication;
- Have a paraffin-embedded tissue block from an archived tumor tissue from the primary tumor or twenty (20) slides of paraffin-embedded tissue available for biomarker analysis;
- Have adequate organ function defined as: absolute neutrophil count ≥1.5× 10^9/L; hemoglobin ≥9 g/dL; platelets ≥75 × 10^9/L; albumin ≥2.5 g/dL; serum bilirubin ≤1.25 ×ULN; aspartate aminotransferase and alanine aminotransferase ≤3 × ULN and serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 mL/min
- Have signed the informed consent form (ICF);
- Women of child-bearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse or consistent and correct use of an acceptable methods of birth control from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication:
Exclusion criteria:
- Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry;
- Had metachronous invasive breast cancer (breast cancers diagnosed at different times);
- Have a prior history of other breast cancer malignancies, including DCIS;
- Are unable to provide archived tumor tissue samples for assay;
- Had prior therapy with an ErbB1 and/or ErbB2 inhibitor; women who experienced a hypersensitivity or allergic reaction to trastuzumab during the first infusion and were unable to complete this infusion are eligible;
- Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication;
- Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
- Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded;
- Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety;
- Have an active or uncontrolled infection;
- Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
- Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;
- Are pregnant or breastfeeding;
- Receive concurrent treatment with an investigational agent; women, who are in follow-up in another clinical trial where the primary endpoint has been met and the interval between assessments is ≥12 months and radiological imaging is not required at these assessments, are eligible;
- Receive concurrent treatment with a selected list of strong inducers and inhibitors of CYP3A4;
- Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication;
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients;
Trial location(s)
Location
GSK Investigational Site
Columbia, Missouri, United States, 65201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Showing 1 - 6 of 430 Results
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
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
2011-21-09
Actual study completion date
2013-17-07
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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