Status and phase
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Identifiers
About
Study E7389-E044-112 is a Phase 1 study designed to assess the safety, tolerability and preliminary efficacy of eribulin-liposomal formulation (E7389-LF) in patients with solid tumors. This dose-escalation study will determine the maximum tolerated dose, dosing schedules tested, the dose schedule regimen with a more favorable tolerability profile, and a preliminary indication of efficacy.
Full description
This is a Phase 1 first-in-human, non-randomized (individuals will not be assigned by chance to study treatments), open-label (individuals will know the identity of study treatments), multicenter, 2-part, dose-escalation study to evaluate the safety, pharmacokinetics (study of what the body does to a drug) of eribulin-LF administered intravenously to patients with solid tumors. Each treatment cycle will be 21 days (Schedule 1) or 28 days (Schedule 1a or 2). Part 1 is the dose-escalation phase, which will be guided by pharmacokinetics and safety. Three to 6 new patients will be enrolled in sequential cohorts (first cohort will receive the starting dose and subsequent cohorts will receive increased doses of eribulin-LF). Enrollment in each cohort will be staggered; the second and third participant in every cohort will not be dosed until the first patient in that cohort completes 2 weeks of Cycle 1. If no dose-limiting toxicities (DLTs) have been observed during the first 2 week of Cycle 1 in the first patient, the second and third patients in the cohort will initiate treatment. Enrollment will be first initiated into cohort 1 of Schedule 1 (dosing on Day 1 of 21 day cycle). Interim analysis will be conducted upon completion of this cohort. The following decisions will be made based upon the results of the interim analysis 1) proceed with escalating to next dose level (cohort 2) of Schedule 1 (dosing on Day 1 of 21 day cycle) and initiate cohort 1 of Schedule 2 (dosing on Day 1 and Day 15 of 28 day cycle), or 2) discontinue plans to evaluate Schedule 2 and initiate Schedule 1a (dosing on Day 1 of 28 day cycle).
After the last patient in each cohort completes Cycle 1, the safety for DLT determination will be evaluated and a decision will be made on whether to escalate the dose in a new cohort of 3 to 6 new patients. Dose escalation will halt when the maximum tolerated dose (MTD) is reached. The total number of patients to be enrolled in Part 1 will depend on the dose level at which the DLT will be achieved. After MTD for each schedule is determined, patients will be enrolled into Expansion Part of the study to confirm safety and tolerability of each dosing schedule. Nine to 12 patients will be treated with MTD for each schedule for 6 cycles. The total study duration for each participant will be approximately 18 months.
Enrollment
Sex
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Inclusion criteria
Exclusion criteria
Females who are pregnant (positive B-hCG [or hCG] test) or breastfeeding.
Participants who have received any anticancer therapy within 21 days prior to study entry for cytotoxic agents (42 days for mitomycin C and nitrosoureas), radiotherapy, hormonal, biological (including humanized antibodies) and targeted agents, or within 30 days for an investigational agent.
Participants who have not recovered from acute toxicities as a result of prior anti-cancer therapy to less than Grade 2, according to Common Terminology Criteria for Adverse Events (CTCAE), except alopecia.
Participants who have previously been treated with eribulin-LF.
Radiation therapy encompassing greater than 30% of the bone marrow.
Major surgery within 21 days prior to enrollment.
Pre-existing peripheral neuropathy greater than CTCAE Grade 1.
Significant cardiovascular impairment, defined as:
Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
Diagnosed with meningeal carcinomatosis.
Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to enrollment. Any symptom(s) attributed to brain metastases must be stable for at least 4 weeks prior to enrollment, and radiographic stability should be confirmed by comparing a brain scan (CT with contrast or MRI with and without contrast) performed during the Screening Period to a brain scan performed at least 4 weeks earlier using the same modality.
Any serious concomitant illness or infection requiring treatment: known active human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C infection (asymptomatic positive serology is not exclusionary).
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
History of drug or alcohol dependency or abuse within approximately the last 2 years or current use of illegal recreational drugs.
Known intolerance to Halaven (eribulin-LF; E7389-LF) or any of the excipients.
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Scheduled for surgery during the study.
Participants with body mass index (BMI) less than 35.
Participants with proven abdominal malignancy with concurrent refractory ascites defined by one of the following criteria:
Participants with concurrent refractory pleural effusion defined by the following criteria:
Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5X the half-life, whichever is longer preceding informed consent.
Primary purpose
Allocation
Interventional model
Masking
62 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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