Phase Ib/II Trial of coPANlisib in Combination With Trastuzumab in HER2-positive Breast Cancer. (Panther Study)

NCT02705859 | Completed Phase 1 DMC

• 1 other identifier: ICORG 15-02
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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).

Conditions

HER2 Positive Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Incidences of adverse events and toxicities.

  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

• 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

• Confirmed tumour response rate as assessed by RECIST criteria version 1.1.

  1.5-2 year

Study Arms (1)

Single Arm

OTHER

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).

Drug: Copanlisib; Drug: Trastuzumab

Interventions

Copanlisib DRUG

Copanlisib is supplied as lyophilized preparation in a 6mL injection vial. The total amount of copanlisib per vial is 60mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Copanlisib will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered first over 60 minutes followed by the infusion of trastuzumab.

Also known as: BAY80-6946

Single Arm

Trastuzumab DRUG

Trastuzumab IV weekly (4mg/kg on Cycle 1 Day 1 followed by 2 mg/kg IV weekly from Day 8).

Also known as: Herceptin

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be included in the study only if they meet all of the following criteria:
• Adult women ≥ 18 years of age.
• Histologically confirmed HER2-positive breast cancer:
• Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive).
• IHC 3+ or FISH/CISH positive on diagnostic breast biopsy or surgical breast resection sample or metastatic disease site biopsy.
• Recurrent incurable or metastatic breast cancer:
• Eligible recurrent disease is recurrent disease that is considered incurable by the treating oncologist. Many local-only recurrences are treated with curative intent; a treatment plan with curative intent for a local-only recurrence would indicate that the patient is not eligible for this clinical trial. A local-only recurrence must be considered incurable by the treating oncologist for the patient to be eligible.
• At least one measurable lesion according to RECIST criteria (Version 1.1). Patients with bone only disease are not eligible.
• Patient has received at least one trastuzumab-based or T-DM1-based treatment regimen in the setting of metastatic disease or incurable locoregional recurrence. A trastuzumab-based or T-DM1-based treatment regimen is considered as any treatment regimen that includes trastuzumab or T-DM1.
• Patients must have had at least 1 line of therapy for metastatic and/or incurable locoregional recurrent disease to be eligible. A patient is eligible regardless of the period of time from adjuvant therapy so long as she has disease that is progressing after at least 1 line of trastuzumab-based therapy in the setting of metastatic disease and/or incurable locoregional recurrence.
• Disease progression during or following at least 1 prior trastuzumab-based or trastuzumab emtansine (T-DM1) based treatment regimen in the setting of metastatic disease or incurable locoregional recurrence.
• ECOG performance status ≤ 2.
• Life expectancy of at least 3 months.
• Availability of fresh tissue and/or archival tumour tissue at screening.
• Women of childbearing potential must agree to use a highly effective method of contraception when sexually active. This applies from signing of the informed consent form until at least 100 days after the last study drug administration. The investigator or a designated associate is required to advise the patient how to achieve an adequate birth control. Highly effective contraception is defined in the study as methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:

You may not qualify if:

• Patients who meet any of the following criteria at the time of screening will be excluded from study registration:
• Known breast cancer involvement of the brain, unless adequately controlled based on the clinical judgement of the treating physician.
• Congestive heart failure \> New York Heart Association (NYHA) class II.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before registration.
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
• Uncontrolled Type I or II diabetes mellitus. Defined as HbA1c \> 8.5% as determined during screening laboratory assessments.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration.
• Non-healing wound, ulcer, or bone fracture.
• Active, clinically serious infections \> CTCAE Grade 2 (CTCAE v4.0).
• Known history of human immunodeficiency virus (HIV) infection.
• Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratory panel. Patients who test positive for Hepatitis B surface Antigen (HBsAg) or Hepatitis B core Antibody (HBcAb) will be eligible if they are negative for HBV-DNA; patients who test positive for anti-HCV antibody will be eligible if they are negative for HCV- RNA.
• Patients with CMV PCR positive.
• Patients with seizure disorder requiring medication.
• Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study treatment.
• Proteinuria of Grade 3 or higher (CTCAE v4.0). Patient will be excluded if \> 2+ on urinalysis (unless 24hr collection shows 24 hour urinary protein \< 3.5g/24hrs).

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (3)

Cancer Trials Ireland Investigative Site

Cork, Ireland

Location

Cancer Trials Ireland Investigative Site

Dublin, Ireland

Location

Cancer Trials Ireland Investigative Site

Galway, Ireland

Location

MeSH Terms

Interventions

copanlisib; Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cancer Trials Ireland Dublin 11, Ireland

  Cancer Trials Ireland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2016
• First Posted: March 11, 2016
• Study Start: April 1, 2016
• Primary Completion: May 1, 2021
• Study Completion: July 1, 2022
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

IE (3)