Trial Outcomes & Findings for Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer (NCT NCT00825734)
NCT ID: NCT00825734
Last Updated: 2014-12-22
Results Overview
Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) - progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
83 participants
Primary outcome timeframe
every 9 weeks until treatment discontinuation or death on study
Results posted on
2014-12-22
Participant Flow
Patients were recruited at multiple dose levels into the Dose Escalation (Phase I) portion of this study to determine the safest dose of this regimen (MTD-Maximum Tolerated Dose). Upon determination of this dose, patients being treated at the MTD proceeded to the Dose Expansion (Phase II) portion of the study and additional patients were recruited
Participant milestones
| Measure |
Dose Level 1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m\^2)
|
Dose Level -1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m\^2)
|
Dose Level 1a
Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)
|
|---|---|---|---|
|
Phase I
STARTED
|
4
|
3
|
3
|
|
Phase I
COMPLETED
|
0
|
0
|
3
|
|
Phase I
NOT COMPLETED
|
4
|
3
|
0
|
|
Phase II
STARTED
|
0
|
0
|
76
|
|
Phase II
COMPLETED
|
0
|
0
|
0
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
76
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
All Patients
n=83 Participants
Patients treated at all dose levels in the Phase I and Phase II portions of the study
: Dose Level 1 (4 patients) Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m\^2)
Dose Level -1 (3 patients) Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m\^2)
Dose Level 1a (76 patients) Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)
|
|---|---|
|
Age, Continuous
|
57 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
82 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
83 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: every 9 weeks until treatment discontinuation or death on studyPopulation: Includes patients treated at the Phase II dose
Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) - progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Sorafenib and Ixabepilone
n=76 Participants
Oral targeted therapy and Systemic Chemotherapy
|
|---|---|
|
Progression-Free Survival (PFS)
|
4.8 months
Interval 3.5 to 6.3
|
SECONDARY outcome
Timeframe: every 9 weeks, up to 6 monthsPopulation: Includes patients treated at the Phase II dose
Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on study. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Sorafenib and Ixabepilone
n=76 Participants
Oral targeted therapy and Systemic Chemotherapy
|
|---|---|
|
6-month Progression-Free Survival
|
42 percentage of participants
|
SECONDARY outcome
Timeframe: every 9 weeks until discontinuation of treatmentPopulation: Includes patients treated at the Phase II dose who were evaluable for response
Objective Response will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST).
Outcome measures
| Measure |
Sorafenib and Ixabepilone
n=68 Participants
Oral targeted therapy and Systemic Chemotherapy
|
|---|---|
|
Objective Response Rate
|
28 patients
|
SECONDARY outcome
Timeframe: every 9 weeks until treatment discontinuation or death on studyPopulation: Includes patients treated at the Phase II dose
Measured from Day 1 of study drug administration to date of death due to any cause.
Outcome measures
| Measure |
Sorafenib and Ixabepilone
n=76 Participants
Oral targeted therapy and Systemic Chemotherapy
|
|---|---|
|
Overall Survival (OS)
|
15.5 months
Interval 11.0 to 20.6
|
SECONDARY outcome
Timeframe: every 9 weeks until treatment discontinuation or unacceptable toxicityPopulation: Patients treated at the Phase II dose
Assessments are made through analysis of reported incidence of treatment-emergent AEs and SAEs.
Outcome measures
| Measure |
Sorafenib and Ixabepilone
n=76 Participants
Oral targeted therapy and Systemic Chemotherapy
|
|---|---|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Neutropenia
|
33 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Febrile neutropenia
|
1 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Anemia
|
27 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Thrombocytopenia
|
22 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Fatigue
|
54 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Nausea/vomiting
|
54 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Rash
|
40 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Neuropathy
|
39 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Anorexia/weight loss
|
36 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Diarrhea
|
33 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Arthralgia/myalgia
|
32 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Alopecia
|
30 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Pain in extremity
|
18 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Hypertension
|
18 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Constipation
|
17 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Dyspnea
|
12 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Hand-foot syndrome
|
12 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Taste alteration
|
11 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Mucositis
|
10 participants
|
|
Number of Patients With Adverse Events as a Measure of of Safety and Tolerability
Pruritus
|
9 participants
|
Adverse Events
Dose Level 1a
Serious events: 6 serious events
Other events: 75 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level 1a
n=76 participants at risk
Includes patients treated at the Phase II dose - Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)
|
|---|---|
|
Renal and urinary disorders
ACUTE RENAL FAILURE
|
1.3%
1/76 • Number of events 1
|
|
Blood and lymphatic system disorders
ANEMIA
|
1.3%
1/76 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.3%
1/76 • Number of events 3
|
|
General disorders
DEATH
|
1.3%
1/76 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
2.6%
2/76 • Number of events 2
|
|
Infections and infestations
INFECTION
|
1.3%
1/76 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
|
1.3%
1/76 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA
|
1.3%
1/76 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
RASH
|
1.3%
1/76 • Number of events 1
|
|
Investigations
WEIGHT LOSS
|
1.3%
1/76 • Number of events 1
|
Other adverse events
| Measure |
Dose Level 1a
n=76 participants at risk
Includes patients treated at the Phase II dose - Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)
|
|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
13.2%
10/76 • Number of events 41
|
|
Investigations
ALKALINE PHOSPHATASE INCREASED
|
5.3%
4/76 • Number of events 16
|
|
Immune system disorders
ALLERGIC REACTION
|
13.2%
10/76 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS
|
9.2%
7/76 • Number of events 26
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
40.8%
31/76 • Number of events 174
|
|
Blood and lymphatic system disorders
ANEMIA
|
35.5%
27/76 • Number of events 119
|
|
Metabolism and nutrition disorders
ANOREXIA
|
36.8%
28/76 • Number of events 76
|
|
Psychiatric disorders
ANXIETY
|
7.9%
6/76 • Number of events 23
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
38.2%
29/76 • Number of events 106
|
|
Musculoskeletal and connective tissue disorders
ASTHENIA
|
18.4%
14/76 • Number of events 99
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
17.1%
13/76 • Number of events 49
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
10.5%
8/76 • Number of events 19
|
|
Skin and subcutaneous tissue disorders
CALLUS
|
6.6%
5/76 • Number of events 41
|
|
General disorders
CHEST PAIN
|
18.4%
14/76 • Number of events 26
|
|
General disorders
CHILLS
|
5.3%
4/76 • Number of events 7
|
|
Gastrointestinal disorders
CONSTIPATION
|
31.6%
24/76 • Number of events 56
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
25.0%
19/76 • Number of events 55
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
7.9%
6/76 • Number of events 7
|
|
Psychiatric disorders
DEPRESSION
|
9.2%
7/76 • Number of events 31
|
|
Skin and subcutaneous tissue disorders
DESQUAMATION
|
7.9%
6/76 • Number of events 11
|
|
Gastrointestinal disorders
DIARRHEA
|
46.1%
35/76 • Number of events 126
|
|
Nervous system disorders
DIZZINESS
|
15.8%
12/76 • Number of events 43
|
|
Gastrointestinal disorders
DRY MOUTH
|
5.3%
4/76 • Number of events 17
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
11.8%
9/76 • Number of events 58
|
|
Gastrointestinal disorders
DYSPEPSIA
|
10.5%
8/76 • Number of events 35
|
|
Gastrointestinal disorders
DYSPHAGIA
|
5.3%
4/76 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
30.3%
23/76 • Number of events 79
|
|
General disorders
EDEMA
|
19.7%
15/76 • Number of events 36
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
7.9%
6/76 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
6.6%
5/76 • Number of events 11
|
|
General disorders
FATIGUE
|
80.3%
61/76 • Number of events 274
|
|
General disorders
FEVER
|
13.2%
10/76 • Number of events 19
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
6.6%
5/76 • Number of events 7
|
|
Vascular disorders
FLUSHING
|
5.3%
4/76 • Number of events 10
|
|
Gastrointestinal disorders
GASTROESOPHAGEAL REFLUX DISEASE
|
6.6%
5/76 • Number of events 17
|
|
Nervous system disorders
HEADACHE
|
17.1%
13/76 • Number of events 29
|
|
Vascular disorders
HOT FLASHES
|
5.3%
4/76 • Number of events 18
|
|
Metabolism and nutrition disorders
HYPERGLYCEMIA
|
10.5%
8/76 • Number of events 31
|
|
Vascular disorders
HYPERTENSION
|
34.2%
26/76 • Number of events 104
|
|
Metabolism and nutrition disorders
HYPOKALEMIA
|
6.6%
5/76 • Number of events 21
|
|
Vascular disorders
HYPOTENSION
|
6.6%
5/76 • Number of events 5
|
|
Infections and infestations
INFECTION
|
11.8%
9/76 • Number of events 10
|
|
Psychiatric disorders
INSOMNIA
|
14.5%
11/76 • Number of events 63
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
42.1%
32/76 • Number of events 114
|
|
Vascular disorders
LYMPHEDEMA
|
5.3%
4/76 • Number of events 8
|
|
Gastrointestinal disorders
MUCOSITIS
|
17.1%
13/76 • Number of events 23
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
19.7%
15/76 • Number of events 42
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
6.6%
5/76 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
NASAL DRAINAGE
|
5.3%
4/76 • Number of events 8
|
|
Gastrointestinal disorders
NAUSEA
|
51.3%
39/76 • Number of events 141
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
47.4%
36/76 • Number of events 115
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
30.3%
23/76 • Number of events 88
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
|
15.8%
12/76 • Number of events 46
|
|
Nervous system disorders
PERIPHERAL NEUROPATHY
|
53.9%
41/76 • Number of events 255
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
13.2%
10/76 • Number of events 21
|
|
General disorders
Pain
|
9.2%
7/76 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
RASH
|
53.9%
41/76 • Number of events 158
|
|
Respiratory, thoracic and mediastinal disorders
SINUSITIS
|
6.6%
5/76 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
SORE THROAT
|
7.9%
6/76 • Number of events 11
|
|
Cardiac disorders
TACHYCARDIA
|
7.9%
6/76 • Number of events 19
|
|
Nervous system disorders
TASTE ALTERATION
|
13.2%
10/76 • Number of events 50
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
30.3%
23/76 • Number of events 65
|
|
Respiratory, thoracic and mediastinal disorders
UPPER RESPIRATORY INFECTION
|
6.6%
5/76 • Number of events 7
|
|
Gastrointestinal disorders
VOMITING
|
26.3%
20/76 • Number of events 37
|
|
Investigations
WEIGHT LOSS
|
14.5%
11/76 • Number of events 23
|
Additional Information
John D. Hainsworth, MD
Sarah Cannon Research Institute
Phone: 1-877-691-7274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER