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

NCT01392521 | Completed Phase 1

• 2 other identifiers: 128762010-024082-45
• Study Type: interventional
• Target: 64
• Locations: 3 countries
• Sites: 8

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. 1.What are the side effects of the combination of Copanlisib and Refametinib (BAY86-9766)when given together at different/increasing dose levels?
2. 2.What dose level of Copanlisib and Refametinib (BAY86-9766) should be tested in future clinical research studies?
3. 3.How much Copanlisib is in the blood at specific times after administration and does adding Refametinib (BAY86-9766) have an affect?
4. 4.How much Refametinib (BAY86-9766) is in the blood at specific times after administration and does adding Copanlisib have an affect?
5. 5.Does the combination of Refametinib (BAY86-9766) and Copanlisib have an effect on tumors?

Conditions

Neoplasms

Keywords

Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose

  2 years

• Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)

  At day 15

• Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib

  At day 15

Secondary Outcomes (4)

• Tumor Response as measured by RECIST 1.1 criteria

  3 years

• Biomarker evaluation including analysis of pathway activation in blood and plasma

  3 years

• Tumor Response as measured by FDG-PET at MTD and expansion cohort(s)

  3 years

• Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies

  3 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: Copanlisib + Refametinib (BAY86-9766)

Interventions

Copanlisib + Refametinib (BAY86-9766) 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.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (8)

Unknown Facility

Scottsdale, Arizona, 85260, United States

Location

Unknown Facility

Las Vegas, Nevada, 89169, United States

Location

Unknown Facility

Greenville, South Carolina, 29605, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Tyler, Texas, 75702, United States

Location

Unknown Facility

Vancouver, Washington, 98684, United States

Location

Unknown Facility

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Unknown Facility

Rotterdam, 3015 CE, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 32314268 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

copanlisib; N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 12, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 17, 2015

Record last verified: 2015-04

Locations

US (6); NL (1); DE (1)