Clinical trial NCT01117623: Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Official title: Open Label, Phase I Study to Determine the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetics, and Biomarker Status of BAY73-4506 in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm
Keywords: Oncology patients with advanced disease
BAY73-4506
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-05-05
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: Continuous dosing of BAY73-4506 in patients with advanced cancer


Eligibility criteria: Inclusion Criteria:

* 18 years
* Patients with advanced, histologically or cytologically confirmed solid tumors, malignant lymphomas, or multiple myeloma refractory to any standard therapy
* Radiographical, hematological or clinically evaluable tumor
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Life expectancy of at least 12 weeks
* Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements:

  * Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
* Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

* History of cardiac disease: congestive heart failure (CHF) \> New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
* Uncontrolled hypertension defined as systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 90 mmHg, despite optimal medical management
* History of HIV infection or chronic hepatitis B or C
* Active clinically serious infections (\> Grade 2 NCI Common Terminology Criteria for Adverse Events v3.0)
* Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Patients with brain metastases must not be undergoing acute steroid therapy or steroid taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
* Substance abuse, medical, psychological or social conditions that may interfere with the patient178s participation in the study or evaluation of the study results
* Radiotherapy to the target lesions within 3 weeks prior to Day 1, Cycle 1 (first dose of study drug). (Palliative radiotherapy will be allowed). Radiotherapy to the target lesions during study will be regarded as progressive disease
* Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis and T1\] or any cancer curatively treated \> 3 years prior to study entry.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within first 4 weeks of treatment
measure: Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
measure: Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
measure: Cmax at Steady State During a Dosing Interval (Cmax,ss)
timeFrame: Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
measure: AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
timeFrame: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
Secondary outcomes:
measure: AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
measure: Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
measure: Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
measure: Half-life Associated With the Terminal Slope (T1/2)
timeFrame: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
measure: Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
timeFrame: Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
timeFrame: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
timeFrame: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Ratio of Cmax,ss/Cmax (RACmax)
timeFrame: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Ratio of Cmin,ss/Cmin (RACmin)
timeFrame: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Ratio of AUCt,ss/AUCt (RAAUC)
timeFrame: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Ratio of AUCt,ss/AUC (RLIN)
timeFrame: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
measure: Biomarker Vascular Endothelial Growth Factor (VEGF) Plasma Levels
timeFrame: No data obtained
measure: Biomarker Soluble Vascular Endothelial Growth Factor Receptor 2 (sCEGFR-2) Plasma Levels
timeFrame: No data obtained
Other outcomes:
measure: Tumor Progression in Dose Escalation Cohort
timeFrame: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
measure: Tumor Progression in Expansion Cohort
timeFrame: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
measure: Tumor Response in Dose Escalation Cohort
timeFrame: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
measure: Tumor Response in Expansion Cohort
timeFrame: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Locations:
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: