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

NCT ID: NCT01411410

Last Updated: 2017-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-24
• Study Completion Date: 2015-06-29

Brief Summary

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.

Conditions

Neoplasms

Keywords

phase I; phosphatidylinositol 3΄-kinase (PI3K); paclitaxel; Maximum tolerated Dose

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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.

Copanlisib (BAY80-6946)

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

St Louis, Missouri, United States

New York, New York, United States

Houston, Texas, United States

Countries

United States

Other Identifiers

12874

Identifier Type: -

Identifier Source: org_study_id