Study Completed

Neoplasms

Bayer Identifier:

12876

ClinicalTrials.gov Identifier:

NCT01392521

EudraCT Number:

2010-024082-45

EU CT Number:

Not Available

Phase Ib study of PI3(phosphoinositol 3)-Kinase inhibitor Copanlisib with MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766) in patients with advanced cancer

Trial purpose

The PI3K (phosphoinositol 3-Kinase) inhibitor Copanlisib and the MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766)have both been tested as single agent treatments in other phase I studies. This study will test the combination of these two drugs to try and answer the following questions:
1. What are the side effects of the combination of Copanlisib and Refametinib (BAY86-9766)when given together at different/increasing dose levels?
2. What dose level of Copanlisib and Refametinib (BAY86-9766) should be tested in future clinical research studies?
3. How much Copanlisib is in the blood at specific times after administration and does adding Refametinib (BAY86-9766) have an affect?
4. How much Refametinib (BAY86-9766) is in the blood at specific times after administration and does adding Copanlisib have an affect?
5. Does the combination of Refametinib (BAY86-9766) and Copanlisib have an effect on tumors?

Key Participants Requirements

Sex

Both

Age

18 - N/A

Inclusion Criteria
- Age greater than/equal to 18 years old
- ECOG Performance Status of 0 - 1
- Life expectancy of at least 12 weeks
- Patients with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy or have no standard therapy available
- LVEF (left ventricular ejection fraction) > or = to the lower limit of normal for the institution
- Radiographically or clinically evaluable tumor
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to start of first dose:
-- Hemoglobin > 9.0 g/dL
-- Absolute neutrophil count (ANC) > or = 1500/mm3
-- Platelet count > or = 100,000 /mm3
-- Total bilirubin < or = 1.5 times the upper limit of normal
-- ALT (alanine aminotransferase) and AST (aspartate aminotransferase) < or = 2.5 x upper limit of normal (< or = 5 x upper limit of normal for patients with liver involvement)
-- PT-INR (prothrombin-international normalized ratio) and PTT (partial thromboplastin time) < or = 1.5 times the upper limit of normal
-- Serum creatinine < or = 1.5 times the upper limit of normal
Exclusion Criteria
- History of impaired cardiac function or clinically significant cardiac disease (i.e. congestive heart failure (CHF) NYHA (New York Heart Association) Class III or IV); active coronary artery disease, myocardial infarction within 6 months of study entry; new onset or unstable angina within 3 months of study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy
- Type 1 or type 2 diabetes mellitus or fasting glucose > 125 mg/dL or HgBA1c > or = 7.0
- Use of systemic corticosteroids within 2 weeks of study entry
- History of retinal vein occlusion
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Active clinically serious infection
- Uncontrolled hypertension
- Positive for HIV, or chronic Hepatitis B or C
- Subjects undergoing renal dialysis
- Known bleeding diathesis
- Ongoing substance abuse
- Pregnant or breast-feeding women

Trial summary

Enrollment Goal

Trial Dates

July 2011 - April 2014

Phase

Phase 1

Could I Receive a placebo

Products

Aliqopa (Copanlisib, BAY80-6946)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Klinik für Tumorbiologie Freiburg	Freiburg, 79106, Germany
Completed	Erasmus Medisch Centrum	ROTTERDAM, 3015 CE, Netherlands
Active, not recruiting	University of Texas MD Anderson Cancer Center	Houston, 77030, United States
Completed	Shea Medical Center	Scottsdale, 85260, United States
Completed	Tyler Cancer Center	Tyler, 75702, United States
Completed	Northwest Cancer Specialists, PC	Vancouver, 98684, United States
Completed	Comprehensive Cancer Centers of Nevada	Las Vegas, 89169, United States
Completed	Greenville Health System	Greenville, 29605, United States

Primary Outcome

Maximum Tolerated Dose
Time Frame:
2 years
Safety Issue:
Yes
Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)
Time Frame:
At day 15
Safety Issue:
No
Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib
Time Frame:
At day 15
Safety Issue:
No

Secondary Outcome

Tumor Response as measured by RECIST 1.1 criteria
Time Frame:
3 years
Safety Issue:
No
Biomarker evaluation including analysis of pathway activation in blood and plasma
Time Frame:
3 years
Safety Issue:
No
Tumor Response as measured by FDG-PET at MTD and expansion cohort(s)
Time Frame:
3 years
Safety Issue:
No
Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies
Time Frame:
3 years
Safety Issue:
No

Trial design

Phase Ib trial of the combination of PI3K inhibitor BAY 80-6946 and allosteric-MEK inhibitor BAY 86-9766 in subjects with advanced cancer

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

N/A

Blinding

Open Label

Assignment

Single Group Assignment

Trial Arms

Additional Information

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