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

Boehringer Ingelheim74 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms

Interventions

Vinorelbine 25 mg/m2 weeklyDRUG

Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy

Afatinib 40mg once daily (OD)DRUG

Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease

Paclitaxel 80 mg/m2 weeklyDRUG

Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (27)

Queen Mary Hospital

Outcomes

Primary Outcomes

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.

Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Secondary Outcomes

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.

Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Best Overall Response According to RECIST v1.1 (Regardless of Confirmation)

Data from ClinicalTrials.gov

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Hong Kong, Hong Kong

Prince of Wales Hospital

Shatin, Hong Kong

Sujan Surgical Cancer Hospital

Amravati, India

Tata Memorial Hospital

Maharashtra, India

Curie Manavata Cancer Centre

Maharashtra, India

Central India Cancer Research Institute

Nagpur, India

Ruby Hall Clinic

Pune, India

Regional Cancer Center

Thiruvananthapuram, India

University Clinical Center, Gdansk

Gdansk, Poland

St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"

Kazan', Russia

...and 17 more locations

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.

Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

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.

Time frame: From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression

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.

Time frame: From the first objective response to the time of progression or death, up to 1562 days

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.

Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP)

Change from baseline to end of treatment in systolic blood pressure (SBP).

Time frame: Baseline and End of treatment period, up to 1562 days

Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP)

Change from baseline to end of treatment in diastolic blood pressure (DBP).

Time frame: Baseline and End of treatment period, up to 1562 days

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)

Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days