LUX-Breast 2; Afatinib in HER2 (Human Epidermal Growth Factor Receptor)-Treatment Failures

Breast Neoplasms Clinical Trial

Official title:

LUX-Breast 2; An Open Label, Phase II Trial of Afatinib (BIBW 2992) in Patients With Metastatic HER2-overexpressing Breast Cancer Failing HER2-targeted Treatment in the Neoadjuvant and/or Adjuvant Treatment Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271725
• Other study ID #: 1200.98
• Secondary ID: 2010-021945-29
• Status: Completed
• Phase: Phase 2
• Start date: May 24, 2011
• Est. completion date: March 13, 2017

Study information

• Verified date: March 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The general aim of this study is to investigate the efficacy and safety of afatinib (BIBW 2992) alone and in combination with weekly paclitaxel or weekly vinorelbine (in patients who progress on afatinib monotherapy within this trial) as treatment in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant or adjuvant setting

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: March 13, 2017
• Est. primary completion date: March 13, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Female patients >=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer

2. Stage IV metastatic disease

3. At least one measurable lesion according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1). Skin, bone and brain lesions are considered non-target lesions

4. Must have failed or progressed on either trastuzumab or lapatinib or trastuzumab and lapatinib treatment in the neoadjuvant and/or adjuvant setting

Exclusion criteria:

1. Prior first line therapy for metastatic breast cancer

2. Known pre-existing interstitial lung disease

3. Active brain metastases

4. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to trial treatment.

5. Cardiac left ventricular function with resting ejection fraction of less than 50%.

6. Prior treatment with Epidermal Growth Factor Receptor (EGFR)/HER2-targeted small molecules or antibodies other than trastuzumab and lapatinib in the neoadjuvant or adjuvant setting

7. Prior treatment with paclitaxel in the past 12 months

8. Must not have received prior vinorelbine treatment - Further exclusion criteria apply

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Vinorelbine 25 mg/m2 weekly
Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy
• Afatinib 40mg once daily (OD)
Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease
• Paclitaxel 80 mg/m2 weekly
Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin
India	Sujan Surgical Cancer Hospital	Amravati
India	Curie Manavata Cancer Centre	Maharashtra
India	Tata Memorial Hospital	Maharashtra
India	Central India Cancer Research Institute	Nagpur
India	Ruby Hall Clinic	Pune
India	Regional Cancer Center	Thiruvananthapuram
Poland	University Clinical Center, Gdansk	Gdansk
Russian Federation	St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"	Kazan
Russian Federation	Clinical Oncology Dispensary No. 1, Dept. Chemotherapy	Krasnodar
Russian Federation	N.A. Semashko Central Clinical Hospital, Moscow	Moscow
Russian Federation	SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"	Pyatigorsk
Russian Federation	SBIH "Samara Regional Clinical Oncol. Dispensary", Samara	Samara
Russian Federation	GUZ "Oncological Dispesary #2"	Sochi
Russian Federation	Stavropol Regional Clin. Oncology Dispensary Dept. Oncology	Stavropol
Russian Federation	Yaroslavl Regional Clinical Oncology Hosp. Dept.Chemotherapy	Yaroslavl
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Koo Foundation Sun Yet-Sen Cancer Center	Taipei
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipe Veterans General Hospital	Taipei
United Kingdom	North Devon District Hospital	Barnstaple
United Kingdom	Royal Bournemouth and Christchurch Hospital	Bournemouth
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Charing Cross Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Hong Kong,  India,  Poland,  Russian Federation,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1	Objective response according to RECIST v1.1. Best overall response of confirmed complete response (CR) or confirmed partial response (PR) recorded since first administration of trial medication and until the earliest of disease progression, death or start of next treatment in each part separately. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of participants with OR along with exact 95% Confidence Interval by Clopper and Pearson is presented.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Secondary	Best Overall Response According to RECIST v1.1 (With Confirmation)	Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Secondary	Best Overall Response According to RECIST v1.1 (Regardless of Confirmation)	Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part (without clinical disease assessment) .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Secondary	Progression Free Survival (PFS)	Progression Free Survival is defined as the time from the drug start date to the date of 1st disease progression or death for monotherapy and 2nd disease progression or death from the drug start date of the combination therapy for combination therapy'. Median is calculated from the Kaplan-Meier curve.	From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression
Secondary	Duration of Objective Response According to RECIST v1.1	Duration of objective response, defined as the time from first objective response to the time of progression or death. (regardless of confirmation). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the first objective response to the time of progression or death, up to 1562 days
Secondary	Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher	Percentage of patients with highest common terminology criteria for adverse events (CTCAE) version 3.0 Grade of 3 or higher.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Secondary	Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP)	Change from baseline to end of treatment in systolic blood pressure (SBP).	Baseline and End of treatment period, up to 1562 days
Secondary	Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP)	Change from baseline to end of treatment in diastolic blood pressure (DBP).	Baseline and End of treatment period, up to 1562 days
Secondary	Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values	Number of patient with possibly clinically significant (PCS) laboratory values by functional group (haematology, differentials, coagulation, electrolytes, enzymes, and substrates). Acronyms Used: Prothrombin time-International normalized ratio (PT-INR), Alanine aminotransferase/Glutamic pyruvic transaminase (ALT/GPT) Serum glutamic pyruvic transaminase (SGPT), Aspartate aminotransferase/Glutamic-oxaloacetic transaminase (AST/GOT) Serum glutamic-oxaloacetic transaminase (SGOT)	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

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