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Study of E7389 Liposomal Formulation in Subjects With Solid Tumor

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ClinicalTrials.gov Identifier: NCT03207672
Recruitment Status : Recruiting
First Posted : July 5, 2017
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

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 in the expansion part 1 and adenoid cystic carcinoma (ACC) in the expansion part 2.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: E7389-LF Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 73 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1 Study of E7389 Liposomal Formulation in Subjects With Solid Tumor
Actual Study Start Date : August 18, 2017
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Schedule 1: E7389-LF
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
intravenous infusion

Experimental: Schedule 2: E7389-LF
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
intravenous infusion




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of E7389 liposomal formulation (E7389-LF) [ Time Frame: Cycle 1 (21 days): Schedule 1; Cycle 1 (28 days): Schedule 2 ]
    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).


Secondary Outcome Measures :
  1. Number of participants with any serious adverse event (SAE) [ Time Frame: up to approximately 3 years ]
    The number of participants with any SAE will be assessed as a measure of the safety and tolerability of E7389- liposomal formulation (LF).

  2. Number of participants with any adverse event (AE) [ Time Frame: up to approximately 3 years ]
    The number of participants with any AE will be assessed as a measure of the safety and tolerability of E7389-LF.

  3. Maximum observed concentration (Cmax) of E7389-LF [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic (PK) analyses. Cmax is the highest concentration of drug in the blood that is measured after a dose. DE = Dose Escalation. Exp = Expansion.

  4. Time from dosing to the maximum observed concentration (Tmax) of E7389-LF [ Time Frame: 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 ]
    Blood samples will be collected for PK analyses. Tmax is the time to the highest concentration of drug in the blood that is measured after a dose. DE = Dose Escalation. Exp = Expansion.

  5. Area under the plasma concentration time course profile (AUC) [ Time Frame: 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 ]
    Blood samples will be collected for PK analyses. AUC represents the overall amount of drug in the bloodstream after dosing. DE = Dose Escalation. Exp = Expansion.

  6. Half-life (t1/2) of E7389-LF [ Time Frame: 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 ]
    Blood samples will be collected for PK analyses. t1/2 is the time required for the concentration of the drug to reach half of its original value. DE = Dose Escalation. Exp = Expansion.

  7. Clearance (CL) of E7389-LF [ Time Frame: 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 ]
    Blood samples will be collected for PK analyses. Clearance is the volume of plasma cleared of the drug per unit time. DE = Dose Escalation. Exp = Expansion.

  8. Volume of distribution (Vd) of E7389-LF [ Time Frame: 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 ]
    Blood samples will be collected for PK analyses. Vd is the volume in which a drug is distributed. DE = Dose Escalation. Exp = Expansion.

  9. Objective response rate (ORR) [ Time Frame: up to approximately 3 years ]
    ORR is defined as the percentage of participants who have a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. For target lesions, CR is defined as the disappearance of all target lesions. For non-target lesions, CR is defined as the disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis). Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. For target lesions, PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  10. Progression free survival (PFS) [ Time Frame: up to approximately 3 years ]
    PFS is defined as the time from the date of randomization to the date of the first documentation of disease progression or date of death, whichever occurs first. For target lesions, progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, progressive disease is defined as the unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • Life expectancy of ≥ 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
  • Adequate washout period before study drug administration:

    • Chemotherapy 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 < 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])
    • Platelets ≥ 100,000/mm^3 (≥ 100 × 10^9/Liter [L])
    • Hemoglobin ≥ 9.0 grams (g)/dL
  • Adequate liver function:

    • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤ 1.5
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
    • Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × ULN
  • Expansion-part only: At least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Willing and able to give informed consent and comply with all aspects of the protocol

Exclusion Criteria:

  • 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 > 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 (e.g. > 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 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 (e.g. 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
  • Evidence of clinically significant disease/status (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
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] or hCG test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  • Males with impregnate potential or females of childbearing potential who or whose partner do not agree with medically effective method of contraception throughout the entire study period and for 28 days (90 days for male) after study drug discontinuation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03207672


Contacts
Contact: Customer Joy Department. EJ 81-3-3817-3700 CLNCL@hhc.eisai.co.jp

Locations
Japan
Eisai Trial Site 3 Recruiting
Kashiwa, Chiba, Japan
Eisai Trial Site 1 Recruiting
Chuo-ku, Tokyo, Japan
Eisai Trial Site 4 Not yet recruiting
Koto-ku, Tokyo, Japan
Eisai Trial Site 2 Recruiting
Osaka, Japan
Sponsors and Collaborators
Eisai Co., Ltd.

Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT03207672     History of Changes
Other Study ID Numbers: E7389-J081-114
First Posted: July 5, 2017    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):
E7389 liposomal formulation
dose escalation
maximum tolerated dose
pharmacokinetics