Copanlisib Pharmacodynamic Study

A Phase I Pharmacodynamic Study of Copanlisib (BAY 80-6946) as Monotherapy in Patients With Non-Hodgkin's Lymphoma and Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: Copanlisib (BAY80-6946)

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Bruxelles - Brussel, Belgium, 1000
  • Gent, Belgium, 9000
• France
  • Caen Cedex 5, France, 14076
  • Lille, France, 59037
  • Nice Cedex 2, France, 06102
  • Pierre Benite, France, 69495
• United Kingdom
  • London, United Kingdom, W1G 6AD
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients	Drug: 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: Arm 2; 45 mg and 60 mg for the diabetic patients	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum change from baseline in expression of pathway inhibition (pAKT) in surrogate tissue (platelet rich plasma) during copanlisib monotherapy	Baseline and approximately 2 years
Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy	Baseline and after day 22

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2014
• Primary Completion (Actual): October 4, 2016
• Study Completion (Actual): March 16, 2017

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Actual): June 16, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Solid tumors
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: 16790; 2013-004746-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No