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NCT01554371

Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

Completed Phase 1, PHASE2 Results posted Last updated 3 February 2021
What this trial tests

Phase 1, PHASE2 trial testing Eribulin in Malignant Solid Tumour in 44 participants. Completed in 31 December 2019.

Timeline
27 March 2012
Primary endpoint
31 December 2019
31 December 2019

Quick facts

Lead sponsorUniversity of California, San Francisco
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment44
Start date27 March 2012
Primary completion31 December 2019
Estimated completion31 December 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of California, San Francisco

Who can join

Adults 18 to 80, any sex, with Malignant Solid Tumour or Breast Cancer Nos Metastatic Recurrent. 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.

Maximum Tolerated Dose (MTD) in Participants With Any Solid Tumor (Phase Ib) Primary · Up to 24 months

Standard dose-confirmation design of 3 to 6 participants per cohort (3+3 design) was used to determine the MTD of eribulin in combination with cyclophosphamide for participants with any solid tumor. The highest dose level or MTD is reached when no more than one of six participants experience a Dose Limiting Toxicity (DLTs). A DLT is defined as any treatment-related toxicity in first 28 days of therapy with a grade 3 or 4 non-hematologic toxicity, a grade 4 neutropenia or thrombocytopenia lasting \>7 days or febrile neutropenia, or any clinically significant toxicity grade 2 or higher that requ

Eribulin
GroupValue95% CI
Phase 1b: Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1.4
Cyclophosphamide
GroupValue95% CI
Phase 1b: Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)600
Clinical Benefit Rate for Patients With Advanced Breast Cancer (ABC) (Phase II) Primary · Up to 24 months

The clinical benefit rate is defined as the proportion of participants with confirmed complete response (CR), partial response (PR) and stable disease (SD) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Responses are determined by changes in the largest diameter of the tumor lesions and the shortest diameter in the case of malignant lymph nodes. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter, PR is defined as at least a 30% decrease in the sum of

GroupValue95% CI
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort).135
Number of Participants With Treatment-related Toxicities Secondary · Up to 24 months

Safety of combination of eribulin and cyclophosphamide in participants was assessed by monitoring the frequency of treatment-related toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with an attribute of possibly, probably, or definitely related to treatment. Number of participants by toxicity will be reported.

Nausea
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)3
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)3
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)19
Constipation
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)3
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)0
Fatigue
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)3
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)26
Peripheral sensory neuropathy
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)2
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)15
Anorexia
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)2
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)13
White blood cell decreased
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)2
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)18
Mucositis oral
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)1
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)3
Platelet count decreased
GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)0
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)2
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)5
Number of Participants With Dose Limiting Toxicity (DLT) for Participants With Any Solid Tumor (Phase 1b) Secondary · Up to 24 months

For the purposes of Phase Ib dose escalation, DLTs will be defined as any treatment-related toxicity occurring within the first 21 days of combination therapy as grade 3 or 4 clinically evident non-hematologic toxicity; grade 4 neutropenia or thrombocytopenia lasting \> 7 days or febrile neutropenia; or any clinically significant toxicity grade 2 or higher that requires more than 14 days to resolve.

GroupValue95% CI
Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)0
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid0
Overall Response Rate (ORR) for Participants With Advanced Breast Cancer (Phase II) Secondary · Up to 24 months

The ORR is defined as the proportion of participants displaying a CR or PR per RECIST criteria recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response will depend on the achievement of both measurement and confirmation criteria with CR defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter and PR is defined as at least a 30% dec

GroupValue95% CI
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort).131
Time to Progression for Participants With Advanced Breast Cancer (Phase II) Secondary · Up to 24 months

Time to progression will be evaluated as time from first treatment to tumor progression in weeks. Disease progression will be measured using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (uni-dimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST 1.1 criteria.

GroupValue95% CI
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)16.413.8 – 21.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)
Serious: 0/3 (0%)
Deaths: 1/3
Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)
Serious: 1/3 (33%)
Deaths: 3/3
Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)
Serious: 5/38 (13%)
Deaths: 32/38

Serious adverse events (5 terms)

ReactionSystemPhase 1b: 1.1 mg/m2 Eribul…Phase 1b: 1.4 mg/m2 Eribul…Phase II: Eribulin Combina…
FeverGeneral disorders
AnemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Low HematocritInvestigations
Neutrophil count decreasedInvestigations
Other adverse events (92 terms — click to expand)

ReactionSystemPhase 1b: 1.1 mg/m2 Eribul…Phase 1b: 1.4 mg/m2 Eribul…Phase II: Eribulin Combina…
DyspneaRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Upper respiratory infectionInfections and infestations
Weight LossInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
HypokalemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
DizzinessNervous system disorders
Bone painMusculoskeletal and connective tissue disorders
Non-cardiac chest painGeneral disorders
PainGeneral disorders
Productive coughRespiratory, thoracic and mediastinal disorders
DepressionPsychiatric disorders
Watering eyesEye disorders
Abdominal distensionGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
FallInjury, poisoning and procedural complications
Gastroesophageal reflux diseaseGastrointestinal disorders
Peripheral motor neuropathyNervous system disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
AnxietyPsychiatric disorders
Urinary frequencyRenal and urinary disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
BloatingGastrointestinal disorders
Muscle weakness lower limbMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Postnasal dripRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
Urinary incontinenceRenal and urinary disorders
Urinary urgencyRenal and urinary disorders
Hot flashesVascular disorders
Sinus tachycardiaCardiac disorders
DysphagiaGastrointestinal disorders
Fecal incontinenceGastrointestinal disorders
ToothacheGastrointestinal disorders

Most-reported serious reactions: Fever, Anemia, Febrile neutropenia, Low Hematocrit, Neutrophil count decreased.

Data from ClinicalTrials.gov NCT01554371 adverse events section.

Sponsor's own description

The purpose of this study is to test the safety of eribulin (Halaven™) and cyclophosphamide (Cytoxan®) given together at different doses. This study will look at what effects, good and/or bad, that these drugs have on solid tumors. Eribulin is a drug that has been approved by the FDA for breast cancer that has spread to other parts of the body. Cyclophosphamide has been approved for different types of cancers (including breast cancer). However, the combination of eribulin and cyclophosphamide is considered experimental; that means this combination has not been approved by the FDA. The funding for this study is provided by Eisai Inc., the maker of eribulin.

Publications & conference data

3 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. Evolving approaches to metastatic breast cancer patients pre-treated with anthracycline and taxane.
    Saji S. · · 2013 · cited 11× · PMID 23658121 · DOI 10.1007/s40259-013-0038-1
  3. A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer.
    Gumusay O, Huppert LA, Magbanua MJM, Wabl CA, et al · · 2024 · cited 2× · PMID 37815684 · DOI 10.1007/s10549-023-07073-0

Verify or expand the search:

Other trials of Eribulin

Trials testing the same drug.

Other recruiting trials for Malignant Solid Tumour

Currently open trials in the same condition.

Other University of California, San Francisco trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01554371.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing