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Completed

NCT Number: NCT01392521

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

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?

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

  1. Maximum Tolerated Dose

    Time frame: 2 years

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

    Time frame: At day 15

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

    Time frame: At day 15

Secondary outcomes

  1. Tumor Response as measured by RECIST 1.1 criteria

    Time frame: 3 years

  2. Biomarker evaluation including analysis of pathway activation in blood and plasma

    Time frame: 3 years

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

    Time frame: 3 years

  4. Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies

    Time frame: 3 years

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
Jul 12, 2011
Registry last updated
Apr 17, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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