Trial Outcomes & Findings for Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer (NCT NCT01527487)
NCT ID: NCT01527487
Last Updated: 2016-11-04
Results Overview
One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
76 participants
Primary outcome timeframe
18 weeks
Results posted on
2016-11-04
Participant Flow
This neoadjuvant trial evaluated the combination of eribulin/cyclophosphamide (ErC) versus docetaxel/cyclophosphamide (TC) in women with clinical stage II-III breast cancers. Between JUN 2012 and APR 2014, 76 patients were enrolled.
After a 10-patient lead-in to confirm safety and feasibility of ErC, subsequent patients (66) were randomized 2 to 1 for treatment with: (1) ErC (44 patients) or (2) TC (22 patients). Both regimens were administered every 21 days for 6 cycles followed by surgery.
Participant milestones
| Measure |
Eribulin+Cyclophosphamide: ErC
Eribulin (Er): 1.4 mg/m\^2 by IV infusion (Days 1 and 8); Cyclophosphamide (C): 600 mg/m\^2 by IV infusion (Day 1)
Administered every 21 days for 6 cycles followed by surgery.
|
Docetaxel+Cyclophosphamide: TC
Docetaxel (T): 75 mg/m\^2 by IV infusion (Day 1); Cyclophosphamide (C): 600 mg/m\^2 by IV infusion (Day 1)tandard.
Administered every 21 days for 6 cycles followed by surgery.
|
|---|---|---|
|
Overall Study
STARTED
|
54
|
22
|
|
Overall Study
COMPLETED
|
46
|
15
|
|
Overall Study
NOT COMPLETED
|
8
|
7
|
Reasons for withdrawal
| Measure |
Eribulin+Cyclophosphamide: ErC
Eribulin (Er): 1.4 mg/m\^2 by IV infusion (Days 1 and 8); Cyclophosphamide (C): 600 mg/m\^2 by IV infusion (Day 1)
Administered every 21 days for 6 cycles followed by surgery.
|
Docetaxel+Cyclophosphamide: TC
Docetaxel (T): 75 mg/m\^2 by IV infusion (Day 1); Cyclophosphamide (C): 600 mg/m\^2 by IV infusion (Day 1)tandard.
Administered every 21 days for 6 cycles followed by surgery.
|
|---|---|---|
|
Overall Study
MD Discretion/Lack of Efficacy
|
3
|
4
|
|
Overall Study
Disease Progression
|
4
|
1
|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
Baseline characteristics by cohort
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=54 Participants
Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard;
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
|
Docetaxel+Cyclophosphamide (TC)
n=22 Participants
Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion;
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
51 years
n=7 Participants
|
52 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
54 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
54 participants
n=5 Participants
|
22 participants
n=7 Participants
|
76 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 weeksPopulation: Patients who completed 6 cycles and proceeded to surgery.
One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.
Outcome measures
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=39 Participants
Eribulin (Er): 1.4mg/m\^2 (Days 1 and 8 of each treatment cycle) by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 IV (Day 1 of each treatment cycle) by IV infusion
|
Docetaxel+Cyclophosphamide (TC)
n=20 Participants
Docetaxel (T): 75 mg/m\^2 (Day 1 of each treatment cycle), by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 (Day 1 of each treatment cycle)
|
|---|---|---|
|
Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery
|
18 percentage of surgical patients
|
10 percentage of surgical patients
|
SECONDARY outcome
Timeframe: 43 monthsTreatment-Related Adverse Events occurring in \>= 15% of treated patients
Outcome measures
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=54 Participants
Eribulin (Er): 1.4mg/m\^2 (Days 1 and 8 of each treatment cycle) by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 IV (Day 1 of each treatment cycle) by IV infusion
|
Docetaxel+Cyclophosphamide (TC)
n=22 Participants
Docetaxel (T): 75 mg/m\^2 (Day 1 of each treatment cycle), by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 (Day 1 of each treatment cycle)
|
|---|---|---|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Neutrophil Count Decreased
|
21 participants
|
6 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Fatigue
|
32 participants
|
14 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Alopecia
|
25 participants
|
14 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Nausea
|
26 participants
|
8 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Peripheral Sensory Neuropathy
|
18 participants
|
10 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Constipation
|
15 participants
|
6 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Diarrhea
|
11 participants
|
10 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Anemia
|
12 participants
|
8 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Headache
|
9 participants
|
4 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Dysgeusia
|
8 participants
|
5 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
White Blood Cell Decreased
|
8 participants
|
5 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Myalgia
|
7 participants
|
6 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Hot Flashes
|
7 participants
|
3 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Mucositis
|
5 participants
|
5 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Arthralgia
|
2 participants
|
8 participants
|
|
The Number of Adverse Events as a Measure of Safety and Tolerability.
Edema Limbs
|
2 participants
|
8 participants
|
SECONDARY outcome
Timeframe: 43 monthsPopulation: All patients evaluated/evaluable per RECIST v1.1
Defined as the number of patients with a best response of clinical complete or partial response (cCR or cPR) divided by the number of patients qualified for tumor response analysis per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI or CT. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD;
Outcome measures
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=34 Participants
Eribulin (Er): 1.4mg/m\^2 (Days 1 and 8 of each treatment cycle) by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 IV (Day 1 of each treatment cycle) by IV infusion
|
Docetaxel+Cyclophosphamide (TC)
n=17 Participants
Docetaxel (T): 75 mg/m\^2 (Day 1 of each treatment cycle), by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 (Day 1 of each treatment cycle)
|
|---|---|---|
|
Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy
|
67.6 percentage of participants
|
64.7 percentage of participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: Includes all patients that completed surgery.
Defined as the percent probability that participants had not experienced disease recurrence or died from any cause at 2 years post-surgery, analyzed by Kaplan-Meier methodology.
Outcome measures
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=53 Participants
Eribulin (Er): 1.4mg/m\^2 (Days 1 and 8 of each treatment cycle) by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 IV (Day 1 of each treatment cycle) by IV infusion
|
Docetaxel+Cyclophosphamide (TC)
n=21 Participants
Docetaxel (T): 75 mg/m\^2 (Day 1 of each treatment cycle), by IV infusion
Cyclophosphamide (C): 600 mg/m\^2 (Day 1 of each treatment cycle)
|
|---|---|---|
|
Disease-Free Survival (DFS) at 2 Years
|
82.35 percent probability of survival
Interval 60.15 to 92.85
|
89.06 percent probability of survival
Interval 62.66 to 97.17
|
Adverse Events
Eribulin+Cyclophosphamide (ErC)
Serious events: 4 serious events
Other events: 44 other events
Deaths: 0 deaths
Docetaxel+Cyclophosphamide (TC)
Serious events: 2 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=54 participants at risk
Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
Eribulin: 1.4 mg/m2 IV (Days 1 \& 8), given short (≤15 minute) IV infusion, per institutional standard
Cyclophosphamide: Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
|
Docetaxel+Cyclophosphamide (TC)
n=22 participants at risk
Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
Cyclophosphamide: Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
Docetaxel: Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
5.6%
3/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Infections and infestations
Sepsis
|
1.9%
1/54 • 43 months
|
4.5%
1/22 • 43 months
|
Other adverse events
| Measure |
Eribulin+Cyclophosphamide (ErC)
n=54 participants at risk
Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
Eribulin: 1.4 mg/m2 IV (Days 1 \& 8), given short (≤15 minute) IV infusion, per institutional standard
Cyclophosphamide: Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
|
Docetaxel+Cyclophosphamide (TC)
n=22 participants at risk
Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion
Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard
Cyclophosphamide: Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
Docetaxel: Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
11.1%
6/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
59.3%
32/54 • 43 months
|
63.6%
14/22 • 43 months
|
|
Blood and lymphatic system disorders
ANEMIA
|
33.3%
18/54 • 43 months
|
36.4%
8/22 • 43 months
|
|
Metabolism and nutrition disorders
ANOREXIA
|
5.6%
3/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
3.7%
2/54 • 43 months
|
36.4%
8/22 • 43 months
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
General disorders
ASTHENIA
|
7.4%
4/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
General disorders
CHILLS
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Gastrointestinal disorders
CONSTIPATION
|
29.6%
16/54 • 43 months
|
27.3%
6/22 • 43 months
|
|
Gastrointestinal disorders
DIARRHEA
|
22.2%
12/54 • 43 months
|
45.5%
10/22 • 43 months
|
|
Nervous system disorders
DIZZINESS
|
9.3%
5/54 • 43 months
|
9.1%
2/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Nervous system disorders
DYSGEUSIA
|
13.0%
7/54 • 43 months
|
18.2%
4/22 • 43 months
|
|
Gastrointestinal disorders
DYSPEPSIA
|
16.7%
9/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
7.4%
4/54 • 43 months
|
9.1%
2/22 • 43 months
|
|
General disorders
EDEMA
|
5.6%
3/54 • 43 months
|
36.4%
8/22 • 43 months
|
|
General disorders
FATIGUE
|
74.1%
40/54 • 43 months
|
63.6%
14/22 • 43 months
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
General disorders
FEVER
|
11.1%
6/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Nervous system disorders
HEADACHE
|
20.4%
11/54 • 43 months
|
18.2%
4/22 • 43 months
|
|
General disorders
HOT FLASHES
|
16.7%
9/54 • 43 months
|
13.6%
3/22 • 43 months
|
|
Nervous system disorders
INSOMNIA
|
9.3%
5/54 • 43 months
|
13.6%
3/22 • 43 months
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
27.8%
15/54 • 43 months
|
22.7%
5/22 • 43 months
|
|
Investigations
LYMPHOCYTE COUNT DECREASED
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
General disorders
MALAISE
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Gastrointestinal disorders
MUCOSITIS
|
11.1%
6/54 • 43 months
|
22.7%
5/22 • 43 months
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
16.7%
9/54 • 43 months
|
27.3%
6/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
NAIL CHANGES
|
3.7%
2/54 • 43 months
|
9.1%
2/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
NAIL DISCOLORATION
|
1.9%
1/54 • 43 months
|
13.6%
3/22 • 43 months
|
|
Gastrointestinal disorders
NAUSEA
|
61.1%
33/54 • 43 months
|
36.4%
8/22 • 43 months
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
48.1%
26/54 • 43 months
|
22.7%
5/22 • 43 months
|
|
Nervous system disorders
PARESTHESIA
|
9.3%
5/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Nervous system disorders
PERIPHERAL NEUROPATHY
|
35.2%
19/54 • 43 months
|
45.5%
10/22 • 43 months
|
|
Respiratory, thoracic and mediastinal disorders
POST NASAL DRIP
|
5.6%
3/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
RASH
|
9.3%
5/54 • 43 months
|
9.1%
2/22 • 43 months
|
|
Skin and subcutaneous tissue disorders
SCALP PAIN
|
0.00%
0/54 • 43 months
|
9.1%
2/22 • 43 months
|
|
Nervous system disorders
TASTE ALTERATION
|
9.3%
5/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
5.6%
3/54 • 43 months
|
4.5%
1/22 • 43 months
|
|
Renal and urinary disorders
URINARY TRACT INFECTION
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Gastrointestinal disorders
VOMITING
|
5.6%
3/54 • 43 months
|
0.00%
0/22 • 43 months
|
|
Eye disorders
WATERING EYES
|
3.7%
2/54 • 43 months
|
9.1%
2/22 • 43 months
|
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