Phase 1
Completed N=86
Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Neoplasm
Source: ClinicalTrials.gov NCT01117623 ↗
Enrolled (actual)
86
Serious AEs
50.0%
Results posted
Jan 2015
Primary outcomePrimary: Maximum Tolerated Dose (MTD) — 100 mg
Summary
Continuous dosing of BAY73-4506 in patients with advanced cancer
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) |
100 | — |
| PRIMARY Maximum Observed Plasma Concentration After Single Dose Administration (Cmax) |
0.330; 0.422; 1.25; 1.87; 1.90; 1.38 | — |
| PRIMARY Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC) |
NA; 16.3; 43.7; 52.9; 52.5; 45.2 | — |
| PRIMARY Cmax at Steady State During a Dosing Interval (Cmax,ss) |
1.27; 1.50; 4.27; 3.62; 5.37; NA | — |
| PRIMARY AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss) |
12.9; 18.1; 49.6; 40.6; 60.4; NA | — |
| SECONDARY AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast)) |
7.98; 9.12; 32.7; 33.5; 35.8; 26.8 | — |
| SECONDARY Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D) |
NA; 0.407; 0.437; 0.441; 0.375; 0.452 | — |
| SECONDARY Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D) |
0.0165; 0.0106; 0.0125; 0.0156; 0.0136; 0.0138 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) |
8.00; 2.02; 5.00; 6.00; 3.01; 3.03 | — |
| SECONDARY Half-life Associated With the Terminal Slope (T1/2) |
NA; 41.6; 31.6; 27.7; 23.2; 25.2 | — |
| SECONDARY Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D) |
0.0636; 0.0374; 0.0427; 0.0302; 0.0383; NA | — |
| SECONDARY AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D) |
0.644; 0.452; 0.496; 0.338; 0.431; NA | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) |
2.00; 2.00; 1.25; 2.00; 2.00; NA | — |
| SECONDARY Ratio of Cmax,ss/Cmax (RACmax) |
3.78; 3.34; 3.50; 1.53; 2.84; NA | — |
| SECONDARY Ratio of Cmin,ss/Cmin (RACmin) |
4.82; 34.9; 26.1; 413; 10.9; NA | — |
| SECONDARY Ratio of AUCt,ss/AUCt (RAAUC) |
3.20; 3.78; 3.15; 1.37; 3.61; NA | — |
| SECONDARY Ratio of AUCt,ss/AUC (RLIN) |
NA; 1.53; 1.27; 0.600; 2.20; NA | — |
| SECONDARY Biomarker Vascular Endothelial Growth Factor (VEGF) Plasma Levels |
— | — |
| SECONDARY Biomarker Soluble Vascular Endothelial Growth Factor Receptor 2 (sCEGFR-2) Plasma Levels |
— | — |
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.
Data sourced from ClinicalTrials.gov (NCT01117623). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.