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AzTrials

Medical OncologyPhase 1NCT02253420

COPANLISIB (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study in Advanced Solid Tumor and Non-Hodgkin's Lymphoma Patients

A Phase 1 study testing Copanlisib (BAY80-6946), Itraconazole and Rifampin in people with Medical Oncology, run by Bayer at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Medical Oncology
What is being tested?
Copanlisib (BAY80-6946), Itraconazole and Rifampin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
5 sitesin 2 countries
Study dates
8 Oct 2014to 13 Aug 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 11Show fewer
  • 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 locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Canada4 sites

  • Study site

    Edmonton, Alberta, T6G 1Z2

  • Study site

    Hamilton, Ontario, L8V 5C2

  • Study site

    Toronto, Ontario, M5G 2M9

  • Study site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

United States1 site

  • Study site

    Dallas, Texas, 75230

Other trials in United States

About this study

Official title: 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

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.

Being tested
Copanlisib (BAY80-6946), Itraconazole, Rifampin
Keywords
Phase 1, Advanced solid tumor, non-Hodgkin's lymphoma, PI3 Kinase inhibitor, Drug-drug Interaction
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Copanlisib (BAY80-6946)Drug

    Part 1 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 12mg Cycle 1 Day 15: Single i.v. dose 12 mg Part 2 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 60mg (based on Part 1 data) Cycle 1 Day 15: Single i.v. dose 60mg (based on Part 1 data)

    Part 1 \& Part 2

    Cycle 2 and subsequent cycles:

    Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg

  • ItraconazoleDrug

    Cycle 1 Day 12: 2 x 200 mg itraconazole oral (two doses, 12 hours apart) Cycle 1 Days 13-21: 200 mg itraconazole oral, once daily in the morning

  • RifampinDrug

    Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning

  • Copanlisib (BAY80-6946)Drug

    Cycle 1 Day 1: Single i.v. dose 60mg Cycle 1 Day 15: Single i.v. dose 60mg

    Cycle 2 and subsequent cycles:

    Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg

Study groups in NCT02253420
Study groupRoleWhat they receive
Copanlisib with and without concomitant Itraconazole (Arm A)ExperimentalTo evaluate the effect of Itraconazole on the pharmacokinetics of Copanlisib (BAY80-6946) and safety in patients with advanced solid tumor. Cycle 1 of the study will be conducted in 2 parts: Part 1 and part 2: * Part 1 of Cycle 1: 6 patients will be enrolled and will receive 12 mg of copanlisib on Day 1 and Day 15. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21. * Part 2 of Cycle 1: 20 patients will be enrolled and receive copanlisib doses of either 12 mg, 30 mg or 60 mg on Days 1 and 15 with the same dose administered on both days. Copanlisib dose for Part 2 will be based on safety and copanlisib pharmacokinetics in Part 1. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21. * Cycle 2 and subsequent cycles: All patients will receive copanlisib doses of 60 mg on Days 1, 8 and 15.
Receives: Drug: Copanlisib (BAY80-6946); Drug: Itraconazole
Copanlisib with and without concomitant Rifampin (Arm B)ExperimentalTo evaluate the effect of Rifampin on the pharmacokinetics of Copanlisib (BAY 80-6946) and safety in patients with advanced solid tumor or non-Hodgkin's lymphoma in Cycle 1. Approximately 30 subjects will receive 60mg of copanlisib on Cycle 1 Day 1 and Cycle 1 Day 15. Rifampin will be administered once a day from Cycle 1 Day 10 to Day 21. Holter monitoring will be performed on Cycle 1 Day -1 and Cycle 1 Day 1 to evaluate the effect of copanlisib on the QT/QTc assessment. Cycle 2 and subsequent cycles, all patients will receive copanlisib dose of 60 mg on Days 1, 8 and 15. Holter monitoring will be performed on Cycle 3 Day 1 and Cycle 6 Day 1.
Receives: Drug: Rifampin; Drug: Copanlisib (BAY80-6946)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUC (0-168)

    AUC (0-168): Area under the curve from dosing to 168 h after dosing

    Measured: 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.

  2. AUC

    AUC: Area under the curve

    Measured: 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.

  3. Cmax

    Cmax: Maximum concentration attained after dosing

    Measured: 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.

  4. QTcF

    QTcF: Time-matched largest change of QT interval (Frederica's correction)

    Measured: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

Secondary outcomes (11)

  1. AUC(0-tlast)

    AUC(0-tlast): Area under the curve from dosing to last measurable concentration

    Measured: 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.

  2. tmax

    tmax: Time from dosing to attainment of Cmax

    Measured: 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.

  3. tlast

    tlast: Time from dosing to last measurable concentration

    Measured: 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.

  4. t1/2

    t1/2: Terminal half-life

    Measured: 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.

  5. Urine [AE,ur(0-24)]

    Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration

    Measured: From 0-8 hours and >8 up to 24 hours after the start of copanlisib infusion on Days 1 and 15 of Cycle 1

  6. Number of participants with adverse events as a measure of safety and tolerability

    Safety analysis will be conducted continuously until safety follow-up

    Measured: At approximately 29 months

  7. PR intervals

    Measured: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

  8. QRS intervals

    Measured: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

  9. ECG waveform morphology

    Measured: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

  10. Left ventricular ejection fraction (LVEF)

    MUGA scans

    Measured: 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

  11. QTcB

    QTcB: Bazett's corrected QT interval

    Measured: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2014 (estimated)
  2. Study start8 Oct 2014
  3. Primary completion12 Mar 2018
  4. Study completion13 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02253420
Sponsor's protocol ID
16270
Status last verified
Dec 2020
First submitted
29 Sep 2014
Last updated
14 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Copanlisib (BAY80-6946), Itraconazole and Rifampin in people with Medical Oncology, run by Bayer at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC (0-168) (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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02253420.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2020.

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