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

Neoplasms Clinical Trial

Official title:

Phase Ib Trial of the Combination of PI3K Inhibitor BAY 80-6946 and Allosteric-MEK Inhibitor BAY 86-9766 in Subjects With Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01392521
• Other study ID #: 12876
• Secondary ID: 2010-024082-45
• Status: Completed
• Phase: Phase 1
• First received: June 30, 2011
• Last updated: April 16, 2015
• Start date: July 2011
• Est. completion date: April 2014

Study information

• Verified date: April 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: April 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Copanlisib + Refametinib (BAY86-9766)
Copanlisib will be administered as an IV infusion weekly for 3 weeks in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 4 of Cycle 1.
• Copanlisib + Refametinib (BAY86-9766)
Copanlisib will be administered as an IV infusion weekly in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 6 of Cycle 1 on a 4 day on, 3 day off schedule.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose		2 years	Yes
Primary	Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)		At day 15	No
Primary	Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib		At day 15	No
Secondary	Tumor Response as measured by RECIST 1.1 criteria		3 years	No
Secondary	Biomarker evaluation including analysis of pathway activation in blood and plasma		3 years	No
Secondary	Tumor Response as measured by FDG-PET at MTD and expansion cohort(s)		3 years	No
Secondary	Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies		3 years	No

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