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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01392521
First received: June 30, 2011
Last updated: October 9, 2014
Last verified: October 2014

June 30, 2011
October 9, 2014
July 2011
February 2014   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01392521 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biomarker evaluation including analysis of pathway activation in tumor tissue and blood/plasma [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
Phase Ib Trial of the Combination of PI3K Inhibitor Copanlisib and Allosteric-MEK Inhibitor Copanlisib in Subjects With Advanced Cancer

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?
Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasms
  • 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.
Experimental: Arm 1
Interventions:
  • Drug: Copanlisib + Refametinib (BAY86-9766)
  • Drug: Copanlisib + Refametinib (BAY86-9766)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
64
February 2014
February 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Netherlands
 
NCT01392521
12876, 2010-024082-45
No
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP