NCT02037529

Eribulin Mesylate or Paclitaxel as First- or Second-Line Therapy in Treating Patients With Recurrent Stage IIIC-IV Breast Cancer

Suspended Phase 3 Results posted Last updated 20 August 2024

What this trial tests

Phase 3 trial testing Eribulin Mesylate in Breast Adenocarcinoma in 201 participants. Suspended.

Timeline

17 January 2014

Primary endpoint
11 February 2021

31 October 2024

Quick facts

Lead sponsor	Academic and Community Cancer Research United
Phase	Phase 3
Status	Suspended
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	201
Start date	17 January 2014
Primary completion	11 February 2021
Estimated completion	31 October 2024
Sites	39 locations across United States

Drugs / interventions tested

• Eribulin Mesylate — full drug profile →
• Laboratory Biomarker Analysis — full drug profile →
• Paclitaxel — full drug profile →
• Quality-of-Life Assessment

Conditions studied

• Breast Adenocarcinoma — all drugs for Breast Adenocarcinoma →
• HER2/Neu Negative — all drugs for HER2/Neu Negative →
• Invasive Breast Carcinoma — all drugs for Invasive Breast Carcinoma →
• Stage IIIC Breast Cancer AJCC v7 — all drugs for Stage IIIC Breast Cancer AJCC v7 →

Sponsor

Academic and Community Cancer Research United — full company profile →

Who can join

18 and older, any sex, with Breast Adenocarcinoma or HER2/Neu Negative. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cumulative Dose Level Triggering a Grade 2 or Higher Neuropathy Event. Primary · 6 months

To validate rs7349683 in EPHA5 as a predictor of peripheral neuropathy from treatment with a microtubule targeting agent (i.e., eribulin or paclitaxel) over the first 6 months of treatment we will compare the median cumulative dose level triggering a grade 2 or higher neuropathy event.

Group	Value	95% CI
Arm A (Eribulin)	39.25	33.2 – 75.6
Arm B (Paclitaxel)	3950	2442 – 6186

Mean Change in Patient Reported PRO-CTCAE Primary · 12 weeks

To demonstrate that patient-reported PRO-CTCAE data will be able to detect differences in symptoms between participants treated with eribulin and standard weekly paclitaxel at 12 weeks we will compare the mean change of overall Pro-CTCAE score by treatment arm. The overall Pro-CTCAE score is a normalized score scaled from 20 questions, each with a possible 1-5 patient selection, creating an overall score (0-100) where 0 represents the best outcome and 100 represents the worst possible outcome. The mean change from baseline to week 12 is reported.

Group	Value	95% CI
Arm A (Eribulin)	3.72	± 0.57
Arm B (Paclitaxel)	3.77	± 0.61

Overall Survival (OS) Secondary · 81 months

The primary analysis will use the stratified log-rank tests, as described for overall survival. As a secondary analysis we will use a multivariable Cox proportional hazard model to estimate adjusted hazard ratios for eribulin mesylate over standard weekly paclitaxel, study stratification factors, and covariates for known prognostic factors, including disease free interval and visceral versus non-visceral metastases. Survival functions will be summarized using the Kaplan-Meier method according to treatment group.

Group	Value	95% CI
Arm A (Eribulin)	18.1	15.4 – 22.1
Arm B (Paclitaxel)	16.4	14.5 – 23.3

Objective Tumor Response Rate Secondary · 64 months

Objective tumor response rate is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Group	Value	95% CI
Arm A (Eribulin)	0.14
Arm B (Paclitaxel)	0.21

Duration of Response Secondary · 75 months

Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals. Duration of response is the time between a tumor response and progression.

Group	Value	95% CI
Arm A (Eribulin)	13.7	9.0 – 19.6
Arm B (Paclitaxel)	14.1	8.4 – 19.8

Time to Treatment Failure Secondary · 64 months

Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Group	Value	95% CI
Arm A (Eribulin)	5.3	3.7 – 5.6
Arm B (Paclitaxel)	4.9	3.2 – 5.5

Incidence of Treatment Related Adverse Events Secondary · 64 months

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT). Events determined to be possibly or probably attributed to a medical treatment suggest there is evidence to indicate a causal relationship between the drug and the adverse event. The number of patients that experienced an AE, of any grade, determin

Group	Value	95% CI
Arm A (Eribulin)	94
Arm B (Paclitaxel)	90

Time to New Metastasis Secondary · 81 months

Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Group	Value	95% CI
Arm A (Eribulin)	8.2	5.7 – 16.9
Arm B (Paclitaxel)	8.7	6.0 – 11.3

Progression Free Survival Assessed by RECIST 1.1 Criteria Secondary · 80 months

Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals. Progression free survival time is the time from date of randomization to the date of first progression or death.

Group	Value	95% CI
Arm A (Eribulin)	5.7	5.4 – 7.1
Arm B (Paclitaxel)	5.9	5.3 – 8.3

Patients With Reported Neurotoxicity Secondary · 24 weeks

Additional analyses will include the previously described analysis conducted over the first 24 weeks; a comparison of the incidence of patient-reported maximum score \>= 3 between arms through 12 and 24 weeks using chi-squared testing for each item; and a comparison of the time to patient-reported score \>= 3 between arms using Kaplan-Meier and log-rank analyses. Further, these three endpoints will be compared between patient- and clinician-report overall and within arms using appropriate paired analyses.

Group	Value	95% CI
Arm A (Eribulin)	26
Arm B (Paclitaxel)	31

Validation of PRO-CTCAE Sensory Neuropathy Item Secondary · At baseline, 12, and 24 weeks

The PRO-CTCAE sensory neuropathy items will be further validated by computing Pearson correlations between each item, severity and interference, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20 )sensory scale score at baseline, 12 and 24 weeks.

Baseline - Severity

Group	Value	95% CI
All Patients	0.72

Baseline - interference

Group	Value	95% CI
All Patients	0.67

Week 12 - severity

Group	Value	95% CI
All Patients	0.71

Week 12 - interference

Group	Value	95% CI
All Patients	0.51

Week 24 - severity

Group	Value	95% CI
All Patients	0.79

Week 24 - interference

Group	Value	95% CI
All Patients	0.85

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were followed for 64 months and mortality was followed for 81 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A (Eribulin)

Serious: 30/101 (30%)

Deaths: 80/101

Arm B (Paclitaxel)

Serious: 30/100 (30%)

Deaths: 79/100

Serious adverse events (63 terms)

Reaction	System	Arm A (Eribulin)	Arm B (Paclitaxel)
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Death NOS	General disorders	—	—
Lung infection	Infections and infestations	—	—
Fracture	Injury, poisoning and procedural complications	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Pericardial effusion	Cardiac disorders	—	—
Sinus tachycardia	Cardiac disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Catheter related infection	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Skin infection	Infections and infestations	—	—
Investigations - Other, specify	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neoplasms benign, mal, uncpec - Oth spec	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Thromboembolic event	Vascular disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Chest pain - cardiac	Cardiac disorders	—	—

Other adverse events (228 terms — click to expand)

Reaction	System	Arm A (Eribulin)	Arm B (Paclitaxel)
Fatigue	General disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Neutrophil count decreased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Pain	General disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
White blood cell decreased	Investigations	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Edema limbs	General disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Weight loss	Investigations	—	—
Hypertension	Vascular disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Depression	Psychiatric disorders	—	—
Alkaline phosphatase increased	Investigations	—	—
Dizziness	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Hot flashes	Vascular disorders	—	—
Infections and infestations - Oth spec	Infections and infestations	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—

Most-reported serious reactions: Dyspnea, Hypoxia, Death NOS, Lung infection, Fracture, Febrile neutropenia, Cardiac arrest, Pericardial effusion.

Data from ClinicalTrials.gov NCT02037529 adverse events section.

Sponsor's own description

This randomized phase III trial studies how well eribulin mesylate or paclitaxel work as first- or second-line therapy in treating patients with stage IIIC-IV breast cancer that has come back. Drugs used in chemotherapy, such as eribulin mesylate and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Eribulin in Cancer Treatment.
   Swami U, Shah U, Goel S. · · 2015 · cited 46× · PMID 26262627 · DOI 10.3390/md13085016
2. Software for Administering the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events: Usability Study.
   Schoen MW, Basch E, Hudson LL, Chung AE, et al · · 2018 · cited 22× · PMID 30012546 · DOI 10.2196/10070
3. Efficacy of eribulin in breast cancer: a short report on the emerging new data.
   Eslamian G, Wilson C, Young RJ. · · 2017 · cited 8× · PMID 28243113 · DOI 10.2147/ott.s102638
4. Methods for implementing and reporting the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events to measure patient-reported adverse events in cancer clinical trials.
   Dueck AC, Thanarajasingam G, Rogak L, Mazza GL, et al · · 2025 · cited 3× · PMID 41123546 · DOI 10.1002/cncr.35951