Trial Outcomes & Findings for Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer (NCT NCT00821886)
NCT ID: NCT00821886
Last Updated: 2014-12-22
Results Overview
Proportion of patients who do not exhibit residual invasive breast cancer in breast or axillary lymph nodes at time of surgery
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
average18 months
Results posted on
2014-12-22
Participant Flow
Participant milestones
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Overall Study
STARTED
|
58
|
|
Overall Study
COMPLETED
|
49
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer
Baseline characteristics by cohort
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 Participants
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: average18 monthsPopulation: Patients who underwent surgery per protocol
Proportion of patients who do not exhibit residual invasive breast cancer in breast or axillary lymph nodes at time of surgery
Outcome measures
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=52 Participants
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Pathologic Complete Response (pCR)
|
27 participants
|
SECONDARY outcome
Timeframe: Day 1 of each 3 week cycle up to 6 cycles , and every 9 weeks post-surgery until treatment discontinuationPopulation: Includes eligible patients
Assessment based on the frequency of treatment-related adverse events according to NCI CTCAE criteria v3.0.
Outcome measures
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 Participants
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Vomiting
|
18 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Fatigue
|
54 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Anemia
|
50 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Neutropenia
|
49 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Peripheral neuropathy
|
47 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Leukopenia
|
46 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Nausea
|
45 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Thrombocytopenia
|
40 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Alopecia
|
26 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Diarrhea
|
25 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Constipation
|
21 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Anorexia
|
19 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Arthralgia
|
16 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Dyspnea
|
14 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Myalgia
|
14 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Pain - extremity
|
14 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Dysgeusia
|
13 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
GERD
|
13 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Rash
|
13 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Edema
|
12 participants
|
|
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Febrile neutropenia
|
4 participants
|
SECONDARY outcome
Timeframe: expected average 18 monthsDefined as the interval from the first date of study treatment until the date of tumor recurrence or death from any cause
Outcome measures
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 Participants
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Disease-free Survival
|
NA months
Interval 53.03 to
Median DFS and upper 95% CI not reached at this time point
|
SECONDARY outcome
Timeframe: approximately 48 monthsDefined as the time between Day 1 Cycle 1 to date of death from any cause.
Outcome measures
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 Participants
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Overall Survival
|
NA months
Median OS and 95% CI not reached at this time point
|
Adverse Events
Ixabepilone/Trastuzumab/Carboplatin
Serious events: 17 serious events
Other events: 58 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 participants at risk
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Infections and infestations - Other, MRSA
|
3.4%
2/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Bronchial infection
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Hepatobiliary disorders
Cholecystitis
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Constipation
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Diarrhea
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Duodenal ulcer
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Encephalopathy
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Pregnancy, puerperium and perinatal conditions
Fetal Death
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Fever
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Infections and infestations - Other, surgical incision site infection
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Non-cardiac chest pain
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Peripheral motor neuropathy
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Skin infection
|
1.7%
1/58
Adverse Event analysis includes patients who were enrolled and treated
|
Other adverse events
| Measure |
Ixabepilone/Trastuzumab/Carboplatin
n=58 participants at risk
Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Ixabepilone: Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Trastuzumab: Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
Carboplatin: Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
|
|---|---|
|
General disorders
Fatigue
|
93.1%
54/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Blood and lymphatic system disorders
Anemia
|
86.2%
50/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
84.5%
49/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
81.0%
47/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
79.3%
46/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Nausea
|
77.6%
45/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
69.0%
40/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
44.8%
26/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Diarrhea
|
43.1%
25/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Constipation
|
36.2%
21/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Metabolism and nutrition disorders
Anorexia
|
32.8%
19/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Vomiting
|
31.0%
18/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
27.6%
16/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
24.1%
14/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
24.1%
14/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
24.1%
14/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Dysgeusia
|
22.4%
13/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
22.4%
13/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.4%
13/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Edema
|
20.7%
12/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Vascular disorders
Hot flashes
|
19.0%
11/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Headache
|
17.2%
10/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.5%
9/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
15.5%
9/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Psychiatric disorders
Insomnia
|
15.5%
9/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Metabolism and nutrition disorders
Dehydration
|
13.8%
8/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
12.1%
7/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Mucositis
|
12.1%
7/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Abdominal pain
|
12.1%
7/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Paresthesia
|
12.1%
7/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Nervous system disorders
Dizziness
|
10.3%
6/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
10.3%
6/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Upper respiratory infection
|
10.3%
6/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Investigations
Alanine aminotransferase increased
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Chills
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Fever
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Pain
|
8.6%
5/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Investigations
Aspartate aminotransferase increased
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Eye disorders
Blurred vision
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Psychiatric disorders
Depression
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
General disorders
Non-cardiac chest pain
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Gastrointestinal disorders
Oral pain
|
6.9%
4/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Investigations
Alkaline phosphatase elevated
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Metabolism and nutrition disorders
Hypokalemia
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Vascular disorders
Hypotension
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Infections and infestations
Infection at port site
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, throat pain
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
|
Eye disorders
Eye disorders - Other, vision changes
|
5.2%
3/58
Adverse Event analysis includes patients who were enrolled and treated
|
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 The sponsor can review/embargo results communications prior to public release for a period that is \>60 but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
- Publication restrictions are in place
Restriction type: OTHER