Phase Ib/II Trial of coPANlisib in Combination With Trastuzumab in HER2-positive Breast Cancer. (Panther Study)
- Registration Number
- NCT02705859
- Lead Sponsor
- Cancer Trials Ireland
- Brief Summary
This study is a Phase Ib/II open label, single arm, adaptive multi-centre trial of copanlisib in combination with trastuzumab in pretreated recurrent or metastatic HER2-positive breast cancer.
Patients with HER2 positive, metastatic or incurable recurrent breast cancer, following disease progression during, or after, treatment with at least one systemic treatment regimen in the metastatic or recurrent setting, will be treated with copanlisib (at 30, 45 or 60 mg flat dosing IV weekly - depending on the maximum tolerated dose (MTD) determined in the Phase Ib part of the study) plus trastuzumab (4 mg/kg IV Cycle 1 Day 1 and then 2 mg/kg IV weekly starting from day 8).
- Detailed Description
Phase Ib One of three dose levels of copanlisib is assigned at registration according to the dose escalation scheme.
Phase II The copanlisib dose for the Phase II part of the trial will be based on the MTD established in the Phase Ib part of the study.
Clinical and laboratory parameters will be assessed to evaluate disease response and toxicity of study therapy.
Safety assessments will be performed throughout the study.
Efficacy assessments (radiological examination) will be performed on all patients every 8 weeks for the first 24 weeks and every 12 weeks thereafter.
Following baseline cardiac assessment, cardiac safety monitoring will include physical exam (with New York Heart Association (NYHA) functional classification for patients with diagnosed congestive heart failure) during each cycle, Multigated acquisition (MUGA) scan or Echocardiogram (ECHO) and 12 lead Electrocardiogram (ECG) within 7 days of Day 1 of every third cycle starting at cycle 3 (Cycle 3, Cycle 6, etc.).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 26
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm Copanlisib This study is a Phase Ib/II open label, single arm, adaptive multi-centre trial. Patients with HER2-positive, metastatic or incurable recurrent breast cancer, following disease progression during, or after, treatment with at least one systemic treatment regimen in the metastatic or recurrent setting, will be treated with copanlisib (at 30, 45 or 60 mg flat dosing IV weekly - depending on the maximum tolerated dose (MTD) determined in the Phase Ib part of the study) plus trastuzumab (4 mg/kg IV Cycle 1 Day 1 and then 2 mg/kg IV weekly starting from day 8). Single Arm Trastuzumab This study is a Phase Ib/II open label, single arm, adaptive multi-centre trial. Patients with HER2-positive, metastatic or incurable recurrent breast cancer, following disease progression during, or after, treatment with at least one systemic treatment regimen in the metastatic or recurrent setting, will be treated with copanlisib (at 30, 45 or 60 mg flat dosing IV weekly - depending on the maximum tolerated dose (MTD) determined in the Phase Ib part of the study) plus trastuzumab (4 mg/kg IV Cycle 1 Day 1 and then 2 mg/kg IV weekly starting from day 8).
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose of copanlisib in combination with trastuzumab measured by the incidence of dose limiting toxicity (DLT) of copanlisib in combination with trastuzumab within the 1st cycle at each dose level. 1 year Clinical Benefit Rate, defined as complete response (CR) or partial response (PR) at any time-point on the study; or stable disease (SD) lasting at least 24 weeks based on radiological assessment. 1 year
- Secondary Outcome Measures
Name Time Method Confirmed tumour response rate as assessed by RECIST criteria version 1.1. 1.5-2 year Overall survival 1.5 -2 year Progression-Free Survival (PFS) assessed according to RECIST criteria version 1.1 1.5-2 year To assess the incidence of cardiotoxicity. Cardiac safety monitoring will include physical exam, (with NYHA functional classification for patients with diagnosed congestive heart failure) at each cycle, and MUGA scan or ECHO 1.5-2 year Incidences of adverse events and toxicities. 1.5 - 2 year Time to Treatment Failure (TTF) is defined as time from registration to discontinuation of therapy or add-on of new anti-cancer therapy for any reason (including death, progression and toxicity). 1.5-2 year Duration of response (DR) as assessed by RECIST criteria version 1.1. 1.5-2 year To evaluate the safety and tolerability of this regimen as measured by incidence of adverse events reported and toxicity evaluation as per the NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). 1.5-2 year
Trial Locations
- Locations (1)
Cancer Trials Ireland Investigative Site
🇮🇪Galway, Ireland