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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01392521
First received: June 30, 2011
Last updated: February 25, 2014
Last verified: February 2014
  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?

Condition Intervention Phase
Neoplasms
Drug: Copanlisib + Refametinib (BAY86-9766)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ib Trial of the Combination of PI3K Inhibitor Copanlisib and Allosteric-MEK Inhibitor Copanlisib in Subjects With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 2 years ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Biomarker evaluation including analysis of pathway activation in blood and plasma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Tumor Response as measured by FDG-PET at MTD and expansion cohort(s) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 92
Study Start Date: July 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01392521

Locations
United States, Arizona
Scottsdale, Arizona, United States, 85260
United States, Nevada
Las Vegas, Nevada, United States, 89169
United States, South Carolina
Greenville, South Carolina, United States, 29605
United States, Texas
Houston, Texas, United States, 77030
Tyler, Texas, United States, 75702
United States, Washington
Vancouver, Washington, United States, 98684
Germany
Freiburg, Baden-Württemberg, Germany, 79106
Netherlands
Rotterdam, Netherlands, 3015 CE
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01392521     History of Changes
Other Study ID Numbers: 12876, 2010-024082-45
Study First Received: June 30, 2011
Last Updated: February 25, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United States: Food and Drug Administration

Keywords provided by Bayer:
Safety
Tolerability
Pharmacokinetics

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 21, 2014