Clinical trial NCT02155582: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Hodgkin Lymphoma
Keywords: Solid tumors
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-06-04
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Maximum change from baseline in expression of pathway inhibition (pAKT) in surrogate tissue (platelet rich plasma) during copanlisib monotherapy
timeFrame: Baseline and approximately 2 years
measure: Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy
timeFrame: Baseline and after day 22
Secondary outcomes:
measure: AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy
timeFrame: After day 22
measure: AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug
timeFrame: Approximately 2 years
measure: Maximum change from baseline in insulin during 2 cycles of copanlisib
timeFrame: After day 22
measure: Maximum change from baseline in C-peptide during 2 cycles of copanlisib
timeFrame: After day 22
measure: FDG PET early response (decreased SUVmax compared to baseline) after dosing with copanlisib for non-diabetic patients with detectable FDG tumor uptake at baseline
timeFrame: After day 22
measure: Change from baseline in expression and / or phosphorylation of PI3K pathway proteins in paired tumor biopsies
timeFrame: Baseline and after day 22
Other outcomes:
Locations:
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Caen Cedex 5
country: France
city: Lille
country: France
city: Nice Cedex 2
country: France
city: Pierre Benite
country: France
city: Sutton
country: United Kingdom
state: Surrey
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: