Study Completed

Medical Oncology

Bayer Identifier:

16270

ClinicalTrials.gov Identifier:

NCT02253420

EudraCT Number:

Not Available

EU CT Number:

Not Available

COPANLISIB (BAY80-6946) drug-drug interaction and cardiovascular safety study in advanced solid tumor and non-Hodgkin's lymphoma patients

Trial purpose

To evaluate the effect of itraconazole or rifampin on the absorption, distribution, metabolism and elimination of COPANLISIB (BAY80-6946).

To evaluate the effect of copanlisib on QT/QTc intervals and left ventricular ejection fraction as parameters of cardiovascular safety.

Key Participants Requirements

Sex

All

Age

18 - N/A

Inclusion Criteria
- Male or female patients ≥ 18 years of age with histological or cytological confirmed advanced solid tumors or non-Hodgkin's lymphoma that have progressed on, or failed to respond to, therapies known to provide clinical benefit may be enrolled after signing informed consent.
- Normal left ventricular ejection fraction; adequate liver, renal and bone-marrow functions as assessed by laboratory values.
- Adequate performance status and life expectancy of at least 3 months.
Exclusion Criteria
- Solid-tumor patients with central nervous system (CNS) metastases if treatment completed < 3 months before enrollment or lesions unstable or progressing on MRI scans performed within 1 month of enrollment or unstable symptoms of the CNS metastases.
- Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF greater than NYHA Class II
- Active coronary artery disease or myocardial infarction within the 6 months before study entry; any new-onset angina within the 3 months before study entry or unstable angina; cardiac arrhythmia requiring anti-arrhythmic therapy.
- Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as fasting blood or plasma glucose above 125 mg/dL under 2 separate days, corresponding to 6.94 mmol/L) or HbA1c ≥ 7%.
- Use of systemic including inhaled corticosteroids within the 2 days before the start of study treatment (however, topical steroids are permitted).
- Known presence of human immunodeficiency virus (HIV) infection or active hepatitis (B or C).
- Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical management).
- Anticancer chemotherapy, hormone therapy or immunotherapy within the 4 weeks before the first study treatment or scheduled for administration (of the above) during the study
- History of, or concurrent, interstitial lung disease (ILD) or severely impaired pulmonary function.
- Medications with drug-drug interaction potential for itraconazole which is to be excluded before the study and during Cycle 1 such as CYP3A4 substrates with a narrow therapeutic window or which have the potential to prolong QTc
- Concomitant medication contraindicated for use with rifampin (including, but not limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or tipranavir

Trial summary

Enrollment Goal

Trial Dates

October 2014 - August 2019

Phase

Phase 1

Could I Receive a placebo

Products

Aliqopa (Copanlisib, BAY80-6946)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		Hamilton, L8V 5C2, Canada
Completed		Vancouver, V5Z 4E6, Canada
Completed		Edmonton, T6G 1Z2, Canada
Completed		Toronto, M5G 2M9, Canada
Completed		Dallas, 75230, United States

Primary Outcome

AUC (0–168)
AUC (0–168): Area under the curve from dosing to 168 h after dosing
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
AUC
AUC: Area under the curve
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
Cmax
Cmax: Maximum concentration attained after dosing
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
QTcF
QTcF: Time-matched largest change of QT interval (Frederica’s correction)
Time Frame:
Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Yes

Secondary Outcome

AUC(0–tlast)
AUC(0–tlast): Area under the curve from dosing to last measurable concentration
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
tmax
tmax: Time from dosing to attainment of Cmax
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
tlast
tlast: Time from dosing to last measurable concentration
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
t1/2
t1/2: Terminal half-life
Time Frame:
Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
Safety Issue:
No
Urine [AE,ur(0–24)]
Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration
Time Frame:
From 0–8 hours and >8 up to 24 hours after the start of copanlisib infusion on Days 1 and 15 of Cycle 1
Safety Issue:
No
Number of participants with adverse events as a measure of safety and tolerability
Safety analysis will be conducted continuously until safety follow-up
Time Frame:
At approximately 29 months
Safety Issue:
Yes
PR intervals
Time Frame:
Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Yes
QRS intervals
Time Frame:
Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Yes
ECG waveform morphology
Time Frame:
Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Yes
Left ventricular ejection fraction (LVEF)
MUGA scans
Time Frame:
At baseline, in the last week of Cycle 1, and in the last 2 weeks of Cycle 2, Cycle 3, Cycle 6 and every third cycle (Cycle 9, Cycle 12, etc.) and end of treatment
Safety Issue:
Yes
QTcB
QTcB: Bazett’s corrected QT interval
Time Frame:
Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

Trial design

An open-label non-randomized, Phase 1 study to evaluate the effect of (a) itraconazole or rifampin on the pharmacokinetics of a single intravenous dose of copanlisib and (b) copanlisib on cardiovascular safety in subjects with advanced solid tumors and non-Hodgkin's lymphoma

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Other

Allocation

Non-randomized

Blinding

Open Label

Assignment

Single Group Assignment

Trial Arms

Additional Information

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