Clinical Trials /

Study of E7389 Liposomal Formulation in Subjects With Solid Tumor

NCT03207672

Description:

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 in participants with adenoid cystic carcinoma (ACC), gastric cancer (GC), esophageal cancer (EGC), and small cell lung cancer (SCLC) in the expansion part 2, 3, 4, and 5.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of E7389 Liposomal Formulation in Subjects With Solid Tumor
  • Official Title: An Open-label Phase 1 Study of E7389 Liposomal Formulation in Subjects With Solid Tumor

Clinical Trial IDs

  • ORG STUDY ID: E7389-J081-114
  • NCT ID: NCT03207672

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
E7389-LFSchedule 1: E7389-LF

Purpose

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 in participants with adenoid cystic carcinoma (ACC), gastric cancer (GC), esophageal cancer (EGC), and small cell lung cancer (SCLC) in the expansion part 2, 3, 4, and 5.

Trial Arms

NameTypeDescriptionInterventions
Schedule 1: E7389-LFExperimentalParticipants 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).
  • E7389-LF
Schedule 2: E7389-LFExperimentalParticipants 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).
  • E7389-LF

Eligibility 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) 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).

          -  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 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 < 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 (Expansion-part only: ≥ 8.5 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 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 (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of E7389 liposomal formulation (E7389-LF)
Time Frame:Cycle 1 (21 days): Schedule 1; Cycle 1 (28 days): Schedule 2
Safety Issue:
Description: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

Measure:Number of participants with any serious adverse event (SAE)
Time Frame:up to approximately 3 years
Safety Issue:
Description:The number of participants with any SAE will be assessed as a measure of the safety and tolerability of E7389- liposomal formulation (LF).
Measure:Number of participants with any adverse event (AE)
Time Frame:up to approximately 3 years
Safety Issue:
Description:The number of participants with any AE will be assessed as a measure of the safety and tolerability of E7389-LF.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Blood samples will be collected for PK analyses. Vd is the volume in which a drug is distributed. DE = Dose Escalation. Exp = Expansion.
Measure:Objective response rate (ORR)
Time Frame:up to approximately 3 years
Safety Issue:
Description: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.
Measure:Progression free survival (PFS)
Time Frame:up to approximately 3 years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Eisai Co., Ltd.

Trial Keywords

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

Last Updated

August 31, 2020