Trial Outcomes & Findings for Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006) (NCT NCT00542971)
NCT ID: NCT00542971
Last Updated: 2018-08-23
Results Overview
MTD is dose level where grade 3-4 sorafenib-attributable toxicity in \<2 of 6 participants. Dose-Limiting Toxicity graded according to the NCI Common Toxicity Criteria version 3.0.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
78 participants
Primary outcome timeframe
Twice a week for first two 28 day cycles
Results posted on
2018-08-23
Participant Flow
Recruitment Period: October 2007 to February 2009. All participants were registered at The University of Texas M.D. Anderson Cancer Center.
Of the 78 participants registered on this study, three (3) were excluded prior to receiving treatment.
Participant milestones
| Measure |
Sorafenib + Idarubicin + Ara-C
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Overall Study
STARTED
|
75
|
|
Overall Study
COMPLETED
|
75
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006)
Baseline characteristics by cohort
| Measure |
Sorafenib + Idarubicin + Ara-C
n=75 Participants
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
75 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Twice a week for first two 28 day cyclesPopulation: 10 participants were treated with escalating doses of sorafenib with chemotherapy to establish the feasibility of the combination.
MTD is dose level where grade 3-4 sorafenib-attributable toxicity in \<2 of 6 participants. Dose-Limiting Toxicity graded according to the NCI Common Toxicity Criteria version 3.0.
Outcome measures
| Measure |
Sorafenib + Idarubicin + Ara-C
n=10 Participants
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Maximum Tolerated Dose (MTD)
|
400 milligrams/twice a day (BID)
|
SECONDARY outcome
Timeframe: Baseline to 2 years or disease progression.Complete response was defined by the presence of \< 5% blasts in the bone marrow (BM) with \> 1 x 10\^9/L platelets in the peripheral blood (PB).
Outcome measures
| Measure |
Sorafenib + Idarubicin + Ara-C
n=75 Participants
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Number of Participants With Complete Response
No Complete Response
|
21 Participants
|
|
Number of Participants With Complete Response
Complete Response
|
54 Participants
|
Adverse Events
Sorafenib + Idarubicin + Ara-C
Serious events: 8 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sorafenib + Idarubicin + Ara-C
n=75 participants at risk；n=78 participants at risk
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Infections and infestations
Infection
|
2.6%
2/78 • Number of events 2 • 2 years, 4 months.
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
2.6%
2/78 • Number of events 2 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Diarrhea
|
1.3%
1/78 • Number of events 1 • 2 years, 4 months.
|
|
Cardiac disorders
Hypertension
|
2.6%
2/78 • Number of events 2 • 2 years, 4 months.
|
|
Metabolism and nutrition disorders
Elevated Alanine Aminotransferase
|
1.3%
1/78 • Number of events 1 • 2 years, 4 months.
|
|
Cardiac disorders
Atrial Fibrillation
|
1.3%
1/78 • Number of events 1 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Death
|
3.8%
3/78 • Number of events 3 • 2 years, 4 months.
|
Other adverse events
| Measure |
Sorafenib + Idarubicin + Ara-C
n=75 participants at risk；n=78 participants at risk
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
30.7%
23/75 • Number of events 26 • 2 years, 4 months.
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Cardiac disorders
Hypertension
|
4.0%
3/75 • Number of events 4 • 2 years, 4 months.
|
|
Cardiac disorders
Cardiac Arrhythmia
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Infections and infestations
Febrile Neutropenia
|
36.0%
27/75 • Number of events 40 • 2 years, 4 months.
|
|
Skin and subcutaneous tissue disorders
Rash Hand Foot Reaction
|
12.0%
9/75 • Number of events 11 • 2 years, 4 months.
|
|
Cardiac disorders
Cardiac General
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Metabolism and nutrition disorders
Elevated Alanine Aminotransferase
|
2.7%
2/75 • Number of events 2 • 2 years, 4 months.
|
|
Infections and infestations
Opportunistic Infection
|
16.0%
12/75 • Number of events 12 • 2 years, 4 months.
|
|
Infections and infestations
Infection
|
10.7%
8/75 • Number of events 9 • 2 years, 4 months.
|
|
Skin and subcutaneous tissue disorders
Rash Desquamation
|
20.0%
15/75 • Number of events 15 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Mucositis
|
9.3%
7/75 • Number of events 7 • 2 years, 4 months.
|
|
Cardiac disorders
Left Ventricular Systolic Dysfunction
|
2.7%
2/75 • Number of events 2 • 2 years, 4 months.
|
|
Metabolism and nutrition disorders
Elevated Creatinine
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Blood and lymphatic system disorders
Hemorrhage Bleeding
|
5.3%
4/75 • Number of events 4 • 2 years, 4 months.
|
|
Metabolism and nutrition disorders
Bilirubin
|
8.0%
6/75 • Number of events 6 • 2 years, 4 months.
|
|
Blood and lymphatic system disorders
edema
|
6.7%
5/75 • Number of events 5 • 2 years, 4 months.
|
|
Nervous system disorders
Mood Alteration
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Nausea
|
6.7%
5/75 • Number of events 5 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Anorexia
|
4.0%
3/75 • Number of events 3 • 2 years, 4 months.
|
|
General disorders
Death
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Renal and urinary disorders
Renal Failure
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
General disorders
Pain
|
4.0%
3/75 • Number of events 7 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Colitis
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Constipation
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
General disorders
Tumor Lysis Syndrome
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Nervous system disorders
Seizures
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Cardiac disorders
Hypotension
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Hepatobiliary disorders
Pancreatitis
|
2.7%
2/75 • Number of events 2 • 2 years, 4 months.
|
|
Gastrointestinal disorders
Dysphasia
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Nervous system disorders
Syncope
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
|
Cardiac disorders
Cardiac Ischemia/Infarct
|
1.3%
1/75 • Number of events 1 • 2 years, 4 months.
|
Additional Information
Farhad Ravandi-Kashani, M.D./Associate Professor
The University of MD Anderson Cancer Center
Phone: 713-745-0394
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place