Copanlisib Pharmacodynamic Study

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Non Hodgkin Lymphoma	Drug: Copanlisib (BAY80-6946)	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	63 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	A Phase I Pharmacodynamic Study of Copanlisib (BAY 80-6946) as Monotherapy in Patients With Non-Hodgkin's Lymphoma and Solid Tumors
Actual Study Start Date :	August 12, 2014
Actual Primary Completion Date :	October 4, 2016
Actual Study Completion Date :	March 16, 2017

Arms and Interventions

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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.

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
2. Maximum change from baseline in plasma glucose during 2 cycles of copanlisib monotherapy [ Time Frame: Baseline and after day 22 ]

Secondary Outcome Measures :

1. AUC(0-168) of copanlisib after each copanlisib IV infusion during 2 cycles of copanlisib monotherapy [ Time Frame: After day 22 ]
2. AEs as characterized by type, frequency, severity (as graded by CTCAE) and relationship to study drug [ Time Frame: Approximately 2 years ]
3. Maximum change from baseline in insulin during 2 cycles of copanlisib [ Time Frame: After day 22 ]
4. Maximum change from baseline in C-peptide during 2 cycles of copanlisib [ Time Frame: After day 22 ]
5. 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 ]
6. 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

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Ages Eligible for Study:	18 Years to 100 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Bayer

Investigators

Study Director:	Bayer Study Director	Bayer

More Information

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Additional Information:

Click here and search for drug information provided by the FDA. 

Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product. 

Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT02155582 History of Changes
Other Study ID Numbers:	16790; 2013-004746-42 ( EudraCT Number )
First Posted:	June 4, 2014
Last Update Posted:	June 16, 2017
Last Verified:	June 2017

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Bayer:

Solid tumors

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms	Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases