Copanlisib Pharmacodynamic Study
Primary Purpose
Non Hodgkin Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Copanlisib (BAY80-6946)
Sponsored by
About this trial
This is an interventional other trial for Non Hodgkin Lymphoma focused on measuring Solid tumors
Eligibility Criteria
- Histologically confirmed diagnosis of the following NHL: follicular lymphoma all grades, lymphoplasmacytic lymphoma / Waldenström macroglobulinemia, transformed indolent lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma, or peripheral T-cell lymphoma, relapsed or refractory, with 1 or more prior chemo-immunotherapy- or immunotherapy-based regimen(s) OR
- Advanced and / or refractory solid tumors with high prevalence (≥30%) of PIK3CA or PTEN alteration: Breast and uterine cancers (endometrium cancers but also non-endometrial uterine cancers), lung (squamous cell only), cervical, head and neck, prostate, and ovarian cancers
- Biopsy-accessible tumor
- Male or female patients equal 18 or more years of age
- NHL patients must have at least 1 bi-dimensionally measurable lesion according to the modified Cheson criteria. Patients with solid tumors must have at least 1 solid tumor lesion measurable by computed tomography or magnetic resonance imaging according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria
- Eastern Cooperative Oncology Group performance status 2 or <
- Life expectancy of at least 3 months
- Adequate bone marrow, liver, and renal functions as assessed by laboratory requirements conducted within 7 days before the first dose of study drug
- Left ventricular ejection fraction > or equal the lower limit of normal for the institution
Exclusion Criteria:
- Previous or concurrent cancer that is distinct in primary site or histology from NHL or the solid tumor, for which the patient is enrolled into this study, within 5 years before treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, in situ breast cancer, in situ prostate carcinoma if Gleason score < or equal to 6 and prostate-specific antigen <10 ng/mL, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]
- Known lymphomatous involvement of the brain or leptomeningeal involvement; solid tumor patients with central nervous system (CNS) metastases if treatment completed <3 months before enrollment or lesions unstable or progressing on magnetic resonance imaging scans performed within 1 month of enrollment or unstable symptoms of the CNS metastases
- Any illness or medical condition that is unstable or could jeopardize the safety of the patient or his / her compliance in the study
- Current diagnosis of type 1 or type 2 diabetes mellitus with HbA1c < or equal to 8.5% or fasting blood glucose < or equal to 160 mg/dL
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1
Arm 2
Arm Description
0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients
45 mg and 60 mg for the diabetic patients
Outcomes
Primary Outcome Measures
Maximum change from baseline in expression of pathway inhibition (pAKT) in surrogate tissue (platelet rich plasma) during copanlisib monotherapy
Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy
Secondary Outcome Measures
AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy
AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug
Maximum change from baseline in insulin during 2 cycles of copanlisib
Maximum change from baseline in C-peptide during 2 cycles of copanlisib
FDG PET early response (decreased SUVmax compared to baseline) after dosing with copanlisib for non-diabetic patients with detectable FDG tumor uptake at baseline
Change from baseline in expression and / or phosphorylation of PI3K pathway proteins in paired tumor biopsies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02155582
Brief Title
Copanlisib Pharmacodynamic Study
Official Title
A Phase I Pharmacodynamic Study of Copanlisib (BAY 80-6946) as Monotherapy in Patients With Non-Hodgkin's Lymphoma and Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
August 12, 2014 (Actual)
Primary Completion Date
October 4, 2016 (Actual)
Study Completion Date
March 16, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to analyze what the study drug does to the body and its relationship to drug levels and safety after patients with advanced cancer have been treated with copanlisib in different dose groups.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hodgkin Lymphoma
Keywords
Solid tumors
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
45 mg and 60 mg for the diabetic patients
Intervention Type
Drug
Intervention Name(s)
Copanlisib (BAY80-6946)
Intervention Description
0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients;45 mg and 60 mg for the diabetic patients; Intravenous (IV) infusion over 1 hour. Dosing of copanlisib will be on Days 1, 8, and 15 of each 28 day treatment cycle.
Primary Outcome Measure Information:
Title
Maximum change from baseline in expression of pathway inhibition (pAKT) in surrogate tissue (platelet rich plasma) during copanlisib monotherapy
Time Frame
Baseline and approximately 2 years
Title
Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy
Time Frame
Baseline and after day 22
Secondary Outcome Measure Information:
Title
AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy
Time Frame
After day 22
Title
AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug
Time Frame
Approximately 2 years
Title
Maximum change from baseline in insulin during 2 cycles of copanlisib
Time Frame
After day 22
Title
Maximum change from baseline in C-peptide during 2 cycles of copanlisib
Time Frame
After day 22
Title
FDG PET early response (decreased SUVmax compared to baseline) after dosing with copanlisib for non-diabetic patients with detectable FDG tumor uptake at baseline
Time Frame
After day 22
Title
Change from baseline in expression and / or phosphorylation of PI3K pathway proteins in paired tumor biopsies
Time Frame
Baseline and after day 22
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Histologically confirmed diagnosis of the following NHL: follicular lymphoma all grades, lymphoplasmacytic lymphoma / Waldenström macroglobulinemia, transformed indolent lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma, or peripheral T-cell lymphoma, relapsed or refractory, with 1 or more prior chemo-immunotherapy- or immunotherapy-based regimen(s) OR
Advanced and / or refractory solid tumors with high prevalence (≥30%) of PIK3CA or PTEN alteration: Breast and uterine cancers (endometrium cancers but also non-endometrial uterine cancers), lung (squamous cell only), cervical, head and neck, prostate, and ovarian cancers
Biopsy-accessible tumor
Male or female patients equal 18 or more years of age
NHL patients must have at least 1 bi-dimensionally measurable lesion according to the modified Cheson criteria. Patients with solid tumors must have at least 1 solid tumor lesion measurable by computed tomography or magnetic resonance imaging according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria
Eastern Cooperative Oncology Group performance status 2 or <
Life expectancy of at least 3 months
Adequate bone marrow, liver, and renal functions as assessed by laboratory requirements conducted within 7 days before the first dose of study drug
Left ventricular ejection fraction > or equal the lower limit of normal for the institution
Exclusion Criteria:
Previous or concurrent cancer that is distinct in primary site or histology from NHL or the solid tumor, for which the patient is enrolled into this study, within 5 years before treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, in situ breast cancer, in situ prostate carcinoma if Gleason score < or equal to 6 and prostate-specific antigen <10 ng/mL, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]
Known lymphomatous involvement of the brain or leptomeningeal involvement; solid tumor patients with central nervous system (CNS) metastases if treatment completed <3 months before enrollment or lesions unstable or progressing on magnetic resonance imaging scans performed within 1 month of enrollment or unstable symptoms of the CNS metastases
Any illness or medical condition that is unstable or could jeopardize the safety of the patient or his / her compliance in the study
Current diagnosis of type 1 or type 2 diabetes mellitus with HbA1c < or equal to 8.5% or fasting blood glucose < or equal to 160 mg/dL
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Bruxelles - Brussel
ZIP/Postal Code
1000
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1200
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Caen Cedex 5
ZIP/Postal Code
14076
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Nice Cedex 2
ZIP/Postal Code
06102
Country
France
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
12. IPD Sharing Statement
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Copanlisib Pharmacodynamic Study
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