Overview

This trial is active, not recruiting.

Condition non hodgkin lymphoma (nhl)
Treatment copanlisib (bay80-6946)
Phase phase 1
Sponsor Bayer
Start date August 2014
End date September 2016
Trial size 55 participants
Trial identifier NCT02155582, 16790, 2013-004746-42

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model parallel assignment
Masking open label
Arm
(Experimental)
0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients
copanlisib (bay80-6946)
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.
(Experimental)
45 mg and 60 mg for the diabetic patients
copanlisib (bay80-6946)
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 Outcomes

Measure
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
Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy
time frame: Baseline and after day 22

Secondary Outcomes

Measure
AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy
time frame: After day 22
AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug
time frame: Approximately 2 years
Maximum change from baseline in insulin during 2 cycles of copanlisib
time frame: After day 22
Maximum change from baseline in C-peptide during 2 cycles of copanlisib
time frame: After day 22
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
Change from baseline in expression and / or phosphorylation of PI3K pathway proteins in paired tumor biopsies
time frame: Baseline and after day 22

Eligibility Criteria

Male or female participants from 18 years up to 100 years old.

- 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

Additional Information

Official title A Phase I Pharmacodynamic Study of Copanlisib (BAY 80-6946) as Monotherapy in Patients With Non-Hodgkin's Lymphoma and Solid Tumors
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Bayer.