Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01411410
First received: August 5, 2011
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

This open label Phase 1 study involves treating subjects with advanced cancer with BAY80-6946 in combination with paclitaxel. It will determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of BAY80-6946 in combination with paclitaxel. The trial will involve multiple participating sites from the US. Following determination of the MTD, an expansion cohort of 20 evaluable subjects with breast cancer was planned. Finally, 16 patients have been enrolled to treatment (Cohort 3). A new expansion cohort with modified dosing cohort is now introduced (Cohort 4: breast cancer expansion cohort with modified dosing) in which another 20 subjects are planned to be enrolled to treatment.


Condition Intervention Phase
Neoplasms
Drug: Paclitaxel
Drug: Copanlisib (BAY80-6946)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Adverse event collection [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose, measured by adverse event profile [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    Cmax: maximum drug concentration in plasma after single dose administration

  • Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    Cmax/D: Cmax divided by total dose in [mg]

  • Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    tmax: time to reach maximum drug concentration in plasma after single (first) dose

  • Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification

  • Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    AUC: area under the plasma concentration vs time curve from zero to infinity

  • Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    AUC/D: AUC divided by total dose in [mg]

  • Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by partial AUC values [eg, AUC(0-25)] of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.

  • Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Estimation of percent of dose excreted [unchanged or as metabolites, if relevant) renally during 0 - 25 h after start of BAY80-6946 infusion (AE,ur(0-25)] (for Cohort 4 only) [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
    AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h

  • Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics characterized by volume of distribution (If possible and needed) of Paclitaxel and 6-OH paclitaxel [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing Cmax of Cycle 1 Day 1 and Cycle 1 Day 15 [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]
  • Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing AUC(0-tlast) of Cycle 1 Day 1 and Cycle 1 Day 15 [ Time Frame: Multiple time points up to 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with mutational status [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: No ]
  • Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copanlisib (BAY80-6946)
The treatment of consists of repetitive cycles, each over 4 weeks. It continues until disease progression or limiting toxicity. If paclitaxel is discontinued for toxicity, BAY80-6946 may continue at the discretion of the investigator if a clinical benefit (response or stable disease for 6 months) is noted.
Drug: Paclitaxel

Paclitaxel (80 mg/m2 in Cohort 1, 2 and 3, 90 mg/m2 in Cohort 4) as 60-minute iv infusion once weekly on Days 1, 8, 15 and 22 (Day 22 in Cohort 1, 2 and 3 only) in 28-day cycles

  • The following intravenous premedications are required 30 to 60 minutes before paclitaxel infusion: Dexamethasone (10 mg), diphenhydramine (50 mg) and either cimetidine (300 mg) or ranitidine (50 mg)
  • Alternatively, for premedications other than dexamethasone, the standard institutional regimen is permitted.
Drug: Copanlisib (BAY80-6946)
BAY80-6946 (0.6 mg/kg in Cohort 1, 0.8 mg/kg in Cohort 2, 3 and 4) as 60-minute iv infusion once weekly on Days 2, 9, 16 and 23 (Day 23 in Cohort 1, 2 and 3 only) in 28-day cycles

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have defined tumor classification (ie, TNBC, HER2+ or Luminal) for enrollment. If tumor classification is not available the subject cannot be enrolled. Tumor classification can be based on analysis of archived tumor tissue, or analysis of tumor tissue collected at any time proximal to screening. Subject profile can also be derived from analysis of fresh tumor tissue obtained during screening. Shipment of specimens (archival or fresh tumor tissue, blood, and plasma) to a central lab can take place after subject enrollment.
  • No prior paclitaxel treatment for subjects in the dose escalation phase. MTD cohort expansion subjects may have had prior paclitaxel, but must not have experienced moderate or severe hypersensitivity reactions to the drug. Peripheral neuropathy must be Grade ≤ 1.
  • Histological or cytological documentation of non-hematologic malignant solid tumor, excluding primary brain or spinal tumors. Patients with prior central nervous system metastases are eligible if all of the following apply: -- Definitive treatment for all lesions (eg, surgery, radiation) was completed at least three months prior to enrollment -- All lesions must be stable or improving on MRI scan performed within one month of enrollment -- All symptoms of the prior CNS metastases are stable.
  • At least one measurable lesion or evaluable disease, as per RECIST 1.1
  • ECOG Performance Status Assessment of 0 or 1
  • Life expectancy of at least 12 weeks

Exclusion Criteria:- History of moderate to severe hypersensitivity (allergy) to drugs formulated in Cremophor® EL (polyoxyethylated castor oil), such as vitamin K, cyclosporin for injection concentrate and teniposide for injection concentrate

  • Pre-existing interstitial lung disease and/or severe impaired pulmonary function
  • History of cardiac disease; congestive heart failure (CHF) >NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
  • Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as consistent fasting blood or plasma glucose > 125 mg/dL) or HgBA1c ≥ 7%
  • Active clinically serious infections Grade ≥ 2 (NCI-CTCAE version 4.0), including viral hepatitis
  • Poorly controlled seizure disorder
  • Poorly controlled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
  • Known human immunodeficiency virus (HIV) infection or chronic hepatitis C or B
  • Subjects undergoing renal dialysis
  • Known bleeding diathesis
  • Pregnant or breast feeding women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01411410

Locations
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, New York
New York, New York, United States, 10065
United States, Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01411410     History of Changes
Other Study ID Numbers: 12874
Study First Received: August 5, 2011
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
phase I
phosphatidylinositol 3΄-kinase (PI3K)
paclitaxel
Maximum tolerated Dose

Additional relevant MeSH terms:
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014