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

NCT ID: NCT01392521

Last Updated: 2015-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-04-30

Brief 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?

Conditions

Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

Copanlisib + Refametinib (BAY86-9766)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Scottsdale, Arizona, United States

Las Vegas, Nevada, United States

Greenville, South Carolina, United States

Houston, Texas, United States

Tyler, Texas, United States

Vancouver, Washington, United States

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Rotterdam, , Netherlands

Countries

United States; Germany; Netherlands

References

Ramanathan RK, Von Hoff DD, Eskens F, Blumenschein G Jr, Richards D, Genvresse I, Reschke S, Granvil C, Skubala A, Pena C, Mross K. Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer. Target Oncol. 2020 Apr;15(2):163-174. doi: 10.1007/s11523-020-00714-0.

Reference Type: DERIVED

PMID: 32314268 (View on PubMed)

Other Identifiers

2010-024082-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12876

Identifier Type: -

Identifier Source: org_study_id