Cancer, Solid Tumor
Conditions
Brief summary
The overall purpose of this study is to determine the overall response rate, efficacy and safety of the combination of eribulin and Lenvatinib.
Detailed description
This is a phase II clinical trial of the combination of eribulin, and Lenvatinib. A cycle will be defined as 21 days. Eribulin will be given on days 1 and 8 of each cycle. Lenvatinib will be given daily during each cycle.
Interventions
DRUGEribulin
Will be given by I.V. at 1.4 mg/m2 on day 1 and day 8.
DRUGLenvatinib
Will be taken orally at 20-24 mg daily in each 21 day cycle.
Sponsors
Eisai Inc.
Virginia G. Kaklamani
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IV breast cancer, stage IV NSCLC (Non-Small Cell Lung Cancer) (, stage IV sarcoma * ECOG (Eastern Cooperative Oncology Group) PS (Performance Status) 0-2 * Measurable disease * No more than 4 prior chemotherapeutic regimens for metastatic disease * Patients must be \>/= 18 years. * Patients may not have received eribulin or lenvatinib previously * Patients must have a life expectancy of greater than 12 weeks. * Patients may have had a prior diagnosis of cancer if it has been \> 5 years since their last treatment and are considered free of disease. * Patients must have normal organ and marrow function as defined below: Leukocytes ≥ 3,000/uL Absolute neutrophil count ≥ 1,500/uL Platelets ≥ 100,000/uL Child Pugh score ≤ 10 Patients must be able to swallow and retain oral medication. All patients must have given signed, informed consent prior to registration on study.
Exclusion criteria
* Women who are pregnant or lactating are not eligible for study treatment. * Patients who are undergoing concomitant radiotherapy are NOT eligible for participation. * Patients who are receiving any other investigational agents or concurrent anticancer therapy are NOT eligible for participation. Previous systemic treatment and/or radiation therapy is allowed with a 14 day washout period prior to registration. * Lesions that have been radiated previously cannot be considered target lesions * Prior treatment related side effects must have resolved to \< Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE version 4.03), except alopecia and infertility. * Patients who are taking any herbal (alternative) medicines are NOT eligible for participation. Patients must be off any such medications by the time of registration. * Patients with known brain metastases are NOT eligible for participation unless the brain metastases are treated (either with surgical excision, stereotactic radiosurgery or radiotherapy) and have been stable for at least 4 wks per MR performed, the patient is asymptomatic and has discontinued corticosteroids if taken for that purpose. * Patients with any of the following conditions or complications are NOT eligible for participation: 1. GI tract disease resulting in an inability to take oral medication 2. Malabsorption syndrome 3. Require IV alimentation 4. History of prior surgical procedures affecting absorption 5. Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). 6. Hypersensitivity of any of the components of eribulin or lenvatinib 7. History of significant neurological ( no neuropathy more than grade 2) or psychiatric disorders 8. Significant non neoplastic liver disease (Cirrhosis, active chronic hepatitis) 9. Immunocompromised subjects, including patients with human immunodeficiency virus 10. Significant non neoplastic renal disease 11. Active infection requiring systemic therapy. 12. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment 13. Prolongation of QTc interval to more than 480 milliseconds when electrolyte balance is normal 14. Major surgery within 4 weeks prior to first dose of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Lenvatinib and Eribulin (Phase II) | 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. | Defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) as assessed by independent imaging review. |
| Progression Free Survival | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | Baseline to 50 months | — |
| Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | 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. | Adverse events are graded in the NCI CTCAE version 4.03 scale and reported by number of adverse events per grade |
Countries
United States
Participant flow
Recruitment details
Participants with the following diagnoses will be included: metastatic solid tumors including breast cancer, NSCLC and soft-tissue sarcoma.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Combination Eribulin and Lenvatinib 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. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 19 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Combination Eribulin and Lenvatinib |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 14 |
| ECOG performance status 0 | 17 Percentage |
| ECOG performance status 1 | 9 Percentage |
| ECOG performance status 2 | 3 Percentage |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 5 Participants |
| Tumor history Lung carcinoma | 6 Participants |
| Tumor history Mammary carcinoma | 17 Participants |
| Tumor history Sarcoma | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 4 / 29 |
Outcome results
Primary
Overall Response Rate of Lenvatinib and Eribulin (Phase II)
Defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) as assessed by independent imaging review.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Eribulin and Lenvatinib | Overall Response Rate of Lenvatinib and Eribulin (Phase II) | Partial Response | 7 participants |
| Combination Eribulin and Lenvatinib | Overall Response Rate of Lenvatinib and Eribulin (Phase II) | Stable Disease | 13 participants |
| Combination Eribulin and Lenvatinib | Overall Response Rate of Lenvatinib and Eribulin (Phase II) | Progression of Disease | 3 participants |
Primary
Progression Free Survival
Progression-free survival (PFS) will be defined as the time from the first study treatment to the first occurrence of progression or death.
Time frame: Baseline to 50 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Eribulin and Lenvatinib | Progression Free Survival | 7.4 months |
Secondary
Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03
Adverse events are graded in the NCI CTCAE version 4.03 scale and reported by number of adverse events per grade
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Eribulin and Lenvatinib | Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | Grade 1 | 182 Events |
| Combination Eribulin and Lenvatinib | Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | Grade 2 | 130 Events |
| Combination Eribulin and Lenvatinib | Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | Grade 3 | 57 Events |
| Combination Eribulin and Lenvatinib | Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | Grade 4 | 9 Events |
| Combination Eribulin and Lenvatinib | Lenvatinib and Eribulin Toxicities Will be Graded Using NCI CTCAE Version 4.03 | Grade 5 | 2 Events |
Secondary
Overall Survival Rate
Time frame: Baseline to 50 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Eribulin and Lenvatinib | Overall Survival Rate | 8.2 Months |