A Randomised, Multicentre, Open-label Phase II Trial Investigating Activity of Chemotherapy and Lapatinib and Trastuzumab in Patients With HER2-positive Metastatic Breast Cancer (MBC) Refractory to Anti HER2 Therapies
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Consorzio Oncotech
- Enrollment
- 154
- Locations
- 36
- Primary Endpoint
- Clinical Benefit Rate
- Last Updated
- 9 years ago
Overview
Brief Summary
Recent clinical studies have shown that the combination of lapatinib and trastuzumab has superior antitumor activity compared to either single drug in both neoadjuvant and metastatic setting and is well tolerated. According to this evidence, the combination of lapatinib and trastuzumab today offers a valid chemotherapy-free option, primarily for patients with pre-treated HER2-positive MBC
Detailed Description
The present study is designed to determine the efficacy and safety profile of the combination of lapatinib and trastuzumab (plus endocrinetherapy in ER-positive breast cancer) versus trastuzumab and chemotherapy in heavily pretreated patient population with HER2-positive MBC and to investigate the predictive role of cfDNA for detection of HER2 gene amplification on patients' outcome. The presence of circulating free DNA (cfDNA) for detection of HER2 gene amplification was associated with worse prognosis and seems to allow early response evaluation. However, many aspects of the role of cfDNA detection in patients undergoing molecular target agents such as trastuzumab or lapatinib are not well described. With the availability of improved and standardized techniques for cfDNA detection, it should now be possible to examine several of these important questions within a prospective multicenter study and a striking potential of cfDNA for detection of HER2 gene amplification might enable a more individual and optimized antimetastatic therapy inpatients with cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histological or cytological confirmed and documented adenocarcinoma of the breast with metastatic disease
- •The original tumour specimen must be HER2 IHC 3+ positive or, in case of IHC 2+
- •Life expectancy of \>12 weeks
- •ECOG PS 0-1
- •Measurable disease as defined by RECIST1.1 criteria
- •All patients must have received prior anthracycline-and taxane-based regimens as well as trastuzumab based regimens in either the adjuvant or the metastatic setting. Patients must have been already treated with at least one line of the anti HER2 inhibitor therapy lapatinib for their metastatic breast cancer. A maximum of three previous lines of anti-HER-2 therapies in the metastatic setting are allowed.
- •Adequate haematological function as defined by: ANC 1.5 x 109/L, platelet count 100 x 109/L, haemoglobin 10 g/dL.
- •Adequate renal function, as defined by: creatinine 1.5 x UNL
- •Adequate hepatobiliary function, as defined by the following baseline liver function tests: total serum bilirubin 1.5 upper normal limit (UNL); alanine amino transferase (ALT), aspartate amino transferase (AST) 2.5xUNL; alkaline phosphatase (AP) 2.5xUNL; if total alkaline phosphatase (AP) \> 2.5xUNL, alkaline phosphatase liver fraction must be 2.5xUNL
- •Adequate contraception for all fertile patients
Exclusion Criteria
- •History of persistent Grade ≥ 2 hematologic toxicity resulting from previous systemic therapy
- •Current peripheral neuropathy of NCI-CTCAE, Version 3.0, Grade ≥ 3 at randomization
- •History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- •Bone-only disease, unless a measurable lesion is evident as determined by RECIST v1.1
- •Bone scan, PET scan or plain films are not considered adequate imaging techniques to measure bone lesions. ve
- •Blastic bone lesions are non-measurable.
- •Uncontrolled hypertension (systolic \>150 mm Hg and/or diastolic \>100 mm Hg) or clinically significant (i.e. active) cardiovascular disease.
- •Current dyspnoea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy.
- •Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization.
- •Current severe, uncontrolled systemic disease
Arms & Interventions
lapatinib and trastuzumab
ARM A: Lapatinib and trastuzumab (experimental arm). Patients with hormone receptor (HR) positive breast cancer will also receive endocrine therapy at the physician's discretion (preferred choice with fulvestrant).
Intervention: Lapatinib
lapatinib and trastuzumab
ARM A: Lapatinib and trastuzumab (experimental arm). Patients with hormone receptor (HR) positive breast cancer will also receive endocrine therapy at the physician's discretion (preferred choice with fulvestrant).
Intervention: Trastuzumab
trastuzumab plus chemotherapy
ARM B: Trastuzumab plus chemotherapy (control arm). Any type of chemotherapy in combination with trastuzumab will be allowed at the physician's discretion.
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Clinical Benefit Rate
Time Frame: Clinical Benefit Rate is defined as confirmed complete response plus partial response at any time, plus stable disease up to 24 weeks
To evaluate clinical benefit rate (CBR) for patients treated with lapatinib and trastuzumab and for patients treated with trastuzumab and chemotherapy. CBR is defined as: confirmed complete response (CR) plus partial response (PR) at any time, plus stable disease (SD) for 24 weeks
Secondary Outcomes
- Overall Survival(Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months)
- Progression free survival(Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months)
- Safety and tolerability(Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months)
- Quality of life(Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months)