Copanlisib Pharmacodynamic Study

Non Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02155582
• Other study ID #: 16790
• Secondary ID: 2013-004746-42
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2014
• Last updated: June 15, 2017
• Start date: August 12, 2014
• Est. completion date: March 16, 2017

Study information

• Verified date: June 2017
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: March 16, 2017
• Est. primary completion date: October 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Belgium,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum change from baseline in expression of pathway inhibition (pAKT) in surrogate tissue (platelet rich plasma) during copanlisib monotherapy		Baseline and approximately 2 years
Primary	Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy		Baseline and after day 22
Secondary	AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy		After day 22
Secondary	AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug		Approximately 2 years
Secondary	Maximum change from baseline in insulin during 2 cycles of copanlisib		After day 22
Secondary	Maximum change from baseline in C-peptide during 2 cycles of copanlisib		After day 22
Secondary	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
Secondary	Change from baseline in expression and / or phosphorylation of PI3K pathway proteins in paired tumor biopsies		Baseline and after day 22

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