Study of E7389 Liposomal Formulation in Participants With Solid Tumor

NCT03207672 | Active Not Recruiting Phase 1

• 1 other identifier: E7389-J081-114
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 12

Brief Summary

The maximum tolerated dose (MTD) of E7389 liposomal formulation (E7389-LF) will be determined in the dose escalation part. Safety, pharmacokinetics (PK) and efficacy will be assessed using treatment regimen evaluated in dose escalation part in participants with breast cancer (up to 3 prior regimens of chemotherapy) in the expansion part 1 and in participants with adenoid cystic carcinoma (ACC), gastric cancer (GC), esophageal cancer (EGC), small cell lung cancer (SCLC) and breast cancer (with no prior regimens of chemotherapy) in the expansion part 2, 3, 4, 5 and 6 respectively.

Conditions

Solid Tumor

Keywords

E7389 liposomal formulation; dose escalation; maximum tolerated dose; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of E7389 liposomal formulation (E7389-LF)

  The MTD is defined as the maximum dose with 0 or 1 dose-limiting toxicity (DLT) in 6 participants. DLTs are defined as study drug-related adverse events (AEs) and graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 4.03 occurring during Cycle 1 (Schedule 1: 3 weeks; Schedule 2: 4 weeks) of the Dose Escalation part of the study (DE-part).

  Cycle 1 (21 days): Schedule 1; Cycle 1 (28 days): Schedule 2

Secondary Outcomes (10)

• Number of participants with any serious adverse event (SAE)

  From date of first dose of study drug up to 30 days after last administration of study drug (approximately up to 8 years)

• Number of participants with any adverse event (AE)

  From date of first dose of study drug up to 30 days after last administration of study drug (approximately up to 8 years)

• Maximum observed concentration (Cmax) of E7389-LF

  DE part: predose; 15 minutes (min) after start of infusion (inf); 5 min after end of inf on Cycle 1 Day 1 (C1D1); 0.5, 1, 2, 4, 6, 8, and 24 hours (hr) postdose (from end of inf on C1D1); C1D4; C1D8; C1D10. Exp part: predose and end of inf on C1D1; C1D8

• Time from dosing to the maximum observed concentration (Tmax) of E7389-LF

  DE part: predose; 15 minutes (min) after start of infusion (inf); 5 min after end of inf on Cycle 1 Day 1 (C1D1); 0.5, 1, 2, 4, 6, 8, and 24 hours (hr) postdose (from end of inf on C1D1); C1D4; C1D8; C1D10. Exp part: predose and end of inf on C1D1; C1D8

• Area under the plasma concentration time course profile (AUC)

  DE part: predose; 15 minutes (min) after infusion (inf) start; 5 min after end of inf on Cycle 1 Day 1 (C1D1); 0.5, 1, 2, 4, 6, 8, and 24 hours (hr) postdose (from end of inf on C1D1); C1D4; C1D8; and C1D10. Exp part: predose and end of inf on C1D1; C1D8

Study Arms (2)

Schedule 1: E7389-LF

EXPERIMENTAL

Participants will receive E7389-liposomal formulation (LF) at a starting dose of 1.0 to 2.5 milligrams per meters squared (mg/m\^2), administered as an intravenous (IV) infusion on Day 1 of a 21-day cycle (tri-weekly).

Drug: E7389-LF

Schedule 2: E7389-LF

EXPERIMENTAL

Participants will receive E7389-LF at a starting dose of 1.0 to 1.5 mg/m\^2, administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle (bi-weekly).

Drug: E7389-LF

Interventions

E7389-LF DRUG

intravenous infusion

Schedule 1: E7389-LF; Schedule 2: E7389-LF

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with advanced, nonresectable, or recurrent solid tumor for which no alternative standard therapy or no effective therapy exists
• Expansion-part 1 only: breast cancer with confirmed diagnosis, human epidermal growth factor (HER2) negative (immunohistochemistry \[IHC\] 0/1+, or fluorescence in situ hybridization \[FISH\] negative), prior chemotherapy of anthracycline and taxane (unless contraindicated), and up to 3 prior chemotherapy regimens to advanced or metastatic disease Expansion-part 2 only: nonresectable ACC with confirmed diagnosis and one or more prior chemotherapy regimens (unless contraindicated) Expansion-part 3, 4 and 5 only: nonresectable GC, EGC and SCLC with confirmed diagnosis and 2 or more prior chemotherapy regimens (unless contraindicated) (1 or more prior chemotherapy regimens for EGC participant who received combination therapy of platinum and taxane).
• Ex-part 6 only: breast cancer with confirmed diagnosis, HER2 negative (IHC 0/1+, or FISH negative) and without prior chemotherapy regimens to advanced or metastatic disease. Participants with triple-negative breast cancer (TNBC) who are PD-L1 negative as assessed by the site or who are medically determined by the investigator(s) to be ineligible for treatment with atezolizumab and other immune-checkpoint inhibitors will be included.
• Life expectancy of greater than or equal to (\>=) 12 weeks
• Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) of 0 to 1
• Japanese participants aged \>=20 years at the time of informed consent
• All adverse events (AEs) due to previous anti-cancer therapy have either returned to Grade 0 or 1 except for alopecia and Grade 2 peripheral neuropathy
• Adequate washout period before study drug administration:
• Chemotherapy, hormonal therapy and radiotherapy: 3 weeks or more
• Any therapy with antibody: 4 weeks or more
• Any investigational drug or device: 4 weeks or more
• Blood/platelet transfusion or granulocyte-colony stimulating factor (G-CSF): 2 weeks or more
• Adequate renal function defined as serum creatinine less than (\<) 2.0 milligrams per deciliter (mg/dL) or creatinine clearance \>=40 milliliters per minute (mL/min) per the Cockcroft and Gault formula
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) \>=2,000/millimeters cubed (mm\^3) (\>=2.0 × 10\^3/microliter \[µl\])

You may not qualify if:

• Any of cardiac conditions as follows:
• Heart failure New York Heart Association (NYHA) Class II or above
• Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting study drug, or angina requiring use of nitrates more than once weekly)
• Prolongation of Fridericia's corrected QT (QTcF) interval to greater than (\>) 480 milliseconds (msec)
• History of hypersensitivity reaction by liposomal formulation agent
• Major surgery within 21 days prior to starting study drug
• Previous treatment with eribulin
• Previous radiation therapy encompassing an extensive region including the bone marrow (example, \>30% of bone marrow)
• Known intolerance to the study drug or any of the excipients
• Known to be human immunodeficiency virus (HIV) positive
• Active viral hepatitis (B or C) as demonstrated by positive serology or requiring treatment
• Diagnosed with meningeal carcinomatosis
• Participants with brain or subdural metastases or invasion are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• Expansion-part only: history of active malignancy (except for primary tumor, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ of the bladder or cervix, or early stage gastric/colorectal cancer) within the past 24 months prior to the first dose of study drug

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (12)

Eisai Trial Site 3

Kashiwa, Chiba, Japan

Location

Eisai Trial Site 5

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site 8

Nishinomiya, Hyōgo, Japan

Location

Eisai Trial Site 6

Yokohama, Kanagawa, Japan

Location

Eisai Trial Site 10

Hidaka, Saitama, Japan

Location

Eisai Trial Site 9

Bunkyo-ku, Tokyo, Japan

Location

Eisai Trial Site 1

Chuo-ku, Tokyo, Japan

Location

Eisai Trial Site 4

Koto-ku, Tokyo, Japan

Location

Eisai Trial Site 7

Shinjuku-ku, Tokyo, Japan

Location

Eisai Trial Site 12

Fukuoka, Japan

Location

Eisai Trial Site 11

Kyoto, Japan

Location

Eisai Trial Site 2

Osaka, Japan

Location

Related Publications (2)

• Masuda N, Ono M, Mukohara T, Yasojima H, Shimoi T, Kobayashi K, Harano K, Mizutani M, Tanioka M, Takahashi S, Kogawa T, Suzuki T, Okumura S, Takase T, Nagai R, Semba T, Zhao ZM, Ren M, Yonemori K. Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the breast cancer expansion cohort. Eur J Cancer. 2022 Jun;168:108-118. doi: 10.1016/j.ejca.2022.03.004. Epub 2022 Apr 29.

  PMID: 35500404 DERIVED

• Sato J, Shimizu T, Koyama T, Iwasa S, Shimomura A, Kondo S, Kitano S, Yonemori K, Fujiwara Y, Tamura K, Suzuki T, Takase T, Nagai R, Yamaguchi K, Semba T, Zhao ZM, Ren M, Yamamoto N. Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 May 2;28(9):1783-1791. doi: 10.1158/1078-0432.CCR-21-3518.

  PMID: 35180771 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: July 5, 2017
• Study Start: August 18, 2017
• Primary Completion: July 19, 2018
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 3, 2026

Record last verified: 2025-07

Locations

JP (12)