Phase Ib/II Trial of coPANlisib in Combination With Trastuzumab in HER2-positive Breast Cancer. (Panther Study) (Panther)
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|ClinicalTrials.gov Identifier: NCT02705859|
Recruitment Status : Recruiting
First Posted : March 11, 2016
Last Update Posted : October 18, 2016
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).
|Condition or disease||Intervention/treatment||Phase|
|HER2 Positive Breast Cancer||Drug: Copanlisib Drug: Trastuzumab||Phase 1|
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.).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Clinical Trial of Copanlisib in Combination With Trastuzumab in Pretreated Recurrent or Metastatic HER2-positive Breast Cancer|
|Study Start Date :||April 2016|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||October 2020|
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).
Copanlisib is a novel small molecule PI3K inhibitor being evaluated for the treatment of a wide variety of advanced and refractory malignancies either as a single agent or in combination with other investigational agents.Copanlisib has potent and selective activity against all four Class I PI3K isoforms with IC50s of 0.5-6.4nM in biochemical assays. Notably, copanlisib shows excellent anti-tumour activity in pre-clinical models with an up-regulated PI3Kα pathway suggesting a particular role for it in PIK3CA mutated cancers.
Other Name: BAY80-6946Drug: Trastuzumab
A humanised IgG1 monoclonal antibody
Other Name: Herceptin
- 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. [ Time Frame: 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. [ Time Frame: 1 year ]
- Incidences of adverse events and toxicities. [ Time Frame: 1.5 - 2 year ]
- Overall survival [ Time Frame: 1.5 -2 year ]
- Progression-Free Survival (PFS) assessed according to RECIST criteria version 1.1 [ Time Frame: 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). [ Time Frame: 1.5-2 year ]
- Confirmed tumour response rate as assessed by RECIST criteria version 1.1. [ Time Frame: 1.5-2 year ]
- Duration of response (DR) as assessed by RECIST criteria version 1.1. [ Time Frame: 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). [ Time Frame: 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 [ Time Frame: 1.5-2 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02705859
|Contact: ICORG 60 Fitzwilliam Square||+353 1 6677211|
|Contact: Prof Bryan Hennessy|
|St Vincent's University Hospital||Recruiting|
|Elm Park, Dublin 4, Ireland|
|Contact: Jo Ballott +353 1 221 4000|
|Principal Investigator: Prof John Crown|
|Beaumont University Hospital||Recruiting|
|Beaumont Road, Dublin 9, Ireland|
|Contact: Derval Kehily +353 1 809 3000|
|Principal Investigator: Prof Bryan Hennessy|
|University Hospital Galway||Not yet recruiting|
|Contact: Mary Byrne|
|Contact +353 91 524 222|
|Principal Investigator: Dr Maccon Keane|