Trial Outcomes & Findings for Eribulin and Lenvatinib in Advanced Solid Tumors (NCT NCT02640508)

NCT ID: NCT02640508

Last Updated: 2024-05-09

Results Overview

Defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) as assessed by independent imaging review.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: The overall response rate will be assessed after two cycles of therapy (1 cycle = 3 weeks) until the date of first documentation of disease progression or death (whichever occurs first) over an average of 18 months.
• Results posted on: 2024-05-09

Participant Flow

Participants with the following diagnoses will be included: metastatic solid tumors including breast cancer, NSCLC and soft-tissue sarcoma.

A 10-patient safety run-in phase for each drug combination will be conducted during cycle 1 of the treatment and subjects evaluated with the remainder of subjects enrolled. After the first 10 subjects have been enrolled the phase II enrollment will begin with the aim of enrolling an additional 20 subjects. All surviving subjects who received study drug will be followed for disease progression and survival. Evaluation of the subjects will be conducted as a single group.

Participant milestones

Measure	Lenvatinib and Eribulin Eribulin will be administered on cycle days 1 and 8; Lenvatinib is an orally administered medication given daily throughout each cycle. On days when both drugs are administered, Eribulin will be administered immediately prior to Lenvatinib.
Overall Study STARTED	29
Overall Study Escalation to Higher Dose	0
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	Lenvatinib and Eribulin Eribulin will be administered on cycle days 1 and 8; Lenvatinib is an orally administered medication given daily throughout each cycle. On days when both drugs are administered, Eribulin will be administered immediately prior to Lenvatinib.
Overall Study Death	19
Overall Study Withdrawal by Subject	8
Overall Study Physician Decision	1
Overall Study Lost to Follow-up	1

Baseline Characteristics

Eribulin and Lenvatinib in Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Combination Eribulin and Lenvatinib n=29 Participants Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8. Lenvatinib: Will be taken orally at 20-24 mg daily in each 21 day cycle.
Age, Continuous	56 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants
ECOG performance status 0	17 Percentage n=5 Participants
ECOG performance status 1	9 Percentage n=5 Participants
ECOG performance status 2	3 Percentage n=5 Participants
Tumor history Mammary carcinoma	17 Participants n=5 Participants
Tumor history Lung carcinoma	6 Participants n=5 Participants
Tumor history Sarcoma	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: The overall response rate will be assessed after two cycles of therapy (1 cycle = 3 weeks) until the date of first documentation of disease progression or death (whichever occurs first) over an average of 18 months.

Population: Only 23 patients had evaluable disease as 6 subjects came off study early prior to first assessment due to toxicities.

Defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) as assessed by independent imaging review.

Outcome measures

Measure	Combination Eribulin and Lenvatinib n=23 Participants Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8. Lenvatinib: Will be taken orally at 20-24 mg daily in each 21 day cycle.
Overall Response Rate of Lenvatinib and Eribulin (Phase II) Partial Response	7 participants
Overall Response Rate of Lenvatinib and Eribulin (Phase II) Stable Disease	13 participants
Overall Response Rate of Lenvatinib and Eribulin (Phase II) Progression of Disease	3 participants

PRIMARY outcome

Timeframe: Baseline to 50 months

Progression-free survival (PFS) will be defined as the time from the first study treatment to the first occurrence of progression or death.

Outcome measures

Measure	Combination Eribulin and Lenvatinib n=23 Participants Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8. Lenvatinib: Will be taken orally at 20-24 mg daily in each 21 day cycle.
Progression Free Survival	7.4 months Interval 1.0 to 47.0

SECONDARY outcome

Timeframe: Baseline to 50 months

Outcome measures

Measure	Combination Eribulin and Lenvatinib n=23 Participants Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8. Lenvatinib: Will be taken orally at 20-24 mg daily in each 21 day cycle.
Overall Survival Rate	8.2 Months Interval 1.0 to 47.0

SECONDARY outcome

Timeframe: Safety will be evaluated from the time of registration until 30 days after last dose of treatment, resolution of the related AE or death up to 40 months.

Population: All subjects that received investigational product, including those from Phase 1 that were not included in the analysis of data

Adverse events are graded in the NCI CTCAE version 4.03 scale and reported by number of adverse events per grade

Outcome measures

Measure	Combination Eribulin and Lenvatinib n=29 Participants Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8. Lenvatinib: Will be taken orally at 20-24 mg daily in each 21 day cycle.
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 Grade 1	182 Events
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 Grade 2	130 Events
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 Grade 3	57 Events
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 Grade 4	9 Events
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 Grade 5	2 Events

Adverse Events

Combination Eribulin and Lenvatinib

Serious events: 4 serious events

Other events: 29 other events

Deaths: 19 deaths

Serious adverse events

Measure	Combination Eribulin and Lenvatinib n=29 participants at risk Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. For each cycle: Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8 and Lenvatinib: Will be taken orally at 20-24 mg daily days 1-21 of each 28 day cycle.
Blood and lymphatic system disorders Neutrophil count decreased	13.8% 4/29 • Number of events 5 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Febrile neutropenia	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Colonic perforation	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
General disorders Dehydration	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Dyspepsia	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Musculoskeletal and connective tissue disorders Epistaxis	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Cardiac disorders Hypertension	6.9% 2/29 • Number of events 2 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Nervous system disorders Myalgia	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Nausea	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Thromboembolic event	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Renal and urinary disorders Urinary tract infection	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Infections and infestations Sepsis	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Skin and subcutaneous tissue disorders Palmar-plantar erthrodysestesia syndrome	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.

Other adverse events

Measure	Combination Eribulin and Lenvatinib n=29 participants at risk Eribulin will be given on days 1 and 8. Lenvatinib will be given daily in each 28 day cycle. For each cycle: Eribulin: Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8 and Lenvatinib: Will be taken orally at 20-24 mg daily days 1-21 of each 28 day cycle.
Gastrointestinal disorders Oral mucositis	62.1% 18/29 • Number of events 32 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
General disorders Fatigue	55.2% 16/29 • Number of events 23 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Neutrophil count decrease	34.5% 10/29 • Number of events 25 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Nausea	48.3% 14/29 • Number of events 16 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Vomiting	34.5% 10/29 • Number of events 13 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Cardiac disorders Hypertension	27.6% 8/29 • Number of events 16 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Febrile neutropenia	20.7% 6/29 • Number of events 6 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Anemia	17.2% 5/29 • Number of events 6 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Anorexia	20.7% 6/29 • Number of events 6 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Endocrine disorders Hypothyroidism	17.2% 5/29 • Number of events 5 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Skin and subcutaneous tissue disorders Alopecia	13.8% 4/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Decreased platelet count	13.8% 4/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Decreased white blood cell count	13.8% 4/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Respiratory, thoracic and mediastinal disorders Sore throat	10.3% 3/29 • Number of events 3 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Abdominal Pain	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Hepatobiliary disorders Alanine Amino transferase increased	10.3% 3/29 • Number of events 3 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Hepatobiliary disorders Alkaline Phosphatase increased	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Hepatobiliary disorders Aspartate aminotransferase increased	10.3% 3/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Blood and lymphatic system disorders Increased bilirubin	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Musculoskeletal and connective tissue disorders Bone pain	10.3% 3/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Constipation	6.9% 2/29 • Number of events 3 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Dehydration	10.3% 3/29 • Number of events 4 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Diarrhea	17.2% 5/29 • Number of events 7 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Nervous system disorders Dizziness	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Dry mouth	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Dysgeusia	3.4% 1/29 • Number of events 1 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.
Gastrointestinal disorders Dyspepsia	10.3% 3/29 • Number of events 3 • Adverse events were collected for all subjects from first cycle of the administration of the study drug through the end of the active study follow-up of the study during treatment up to 50 months. No subjects were escalated to a higher dose due to toxicity concerns, so all participants received the same dose.

Additional Information

Virginia Kaklamani, MD

UT Health San Antonio

Phone: 210-450-3838

Email: kaklamani@uthscsa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place