Clinical Trials /

Oral Paclitaxel Trial In Recurrent and Metastatic Breast Cancer As 1st Line Therapy

NCT03315364

Description:

To compare and evaluate the efficacy and safety of Liporaxel® solution (oral paclitaxel) and Taxol® (IV paclitaxel) on recurrent or metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Oral Paclitaxel Trial In Recurrent and Metastatic Breast Cancer As 1st Line Therapy
  • Official Title: A Multicenter, Open-label, Phase II/III Clinical Trial to Evaluate the Efficacy and Safety of Liporaxel® (Oral Paclitaxel) Compared to Taxol® (IV Paclitaxel) as First-line Therapy in Patients With Recurrent or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 107CS-5
  • NCT ID: NCT03315364

Conditions

  • Recurrent or Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Oral paclitaxelLiporaxel®Liporaxel® (oral paclitaxel)
Paclitaxel injectionTaxol®Taxol® (IV paclitaxel)

Purpose

To compare and evaluate the efficacy and safety of Liporaxel® solution (oral paclitaxel) and Taxol® (IV paclitaxel) on recurrent or metastatic breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Liporaxel® (oral paclitaxel)Experimental28 days (4 weeks) will be set as one cycle of administration and Liporaxel® will be administered for 3 weeks, twice a day, every morning and evening (D1, D8, D15) and will take a week off on 4th week. Liproaxel® 200mg/m2 will be orally administered twice a day (morning, evening) 1 hour after meal for D1, D8, D15 of every cycle. 10 hour-interval is recommended for between each administration.
  • Oral paclitaxel
Taxol® (IV paclitaxel)Active Comparator28 days (4 weeks) will be set as one cycle and for every 3 week administration, 1 week off dose period will be given. Taxol® 80mg/m2 will be administered via IV and it must be diluted before drip administration. Dilute with 0.9% sodium chloride injection solution to make final concentration of 0.3-1.2 mg/mL.
  • Paclitaxel injection

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects who are ≥ 19 years of age on the date of written informed consent

          2. Subjects with confirmed diagnosis of recurrent or metastatic breast cancer based on
             histopathology examination (tumor characteristics should be confirmed by histological
             or cytological evaluation):

               -  Subjects are eligible for the study regardless of hormone receptor status (ER/PR
                  positive or negative)

               -  ER/PR(+) is defined as cells expressing hormone receptors >1% in
                  immunohistochemistry (IHC) analysis of collected samples.

          3. Subjects whose tumor sample (primary or metastatic) is confirmed HER-2 negative with
             one of the followings (HER2 test should be performed using samples of metastatic site,
             if metastasis is confirmed and samples can be collected from the metastatic lesions.)

               -  Immunohistochemistry (IHC) 0 or 1+ (for IHC 2+, subjects can be enrolled, if
                  HER2-negative is confirmed by In situ hybridization [ISH].)

               -  In situ hybridization (ISH) with the following results:

                    -  Single-probe average HER2 copy number < 4.0 signals/cell)

                    -  Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number < 4.0
                       signals/cell

          4. Subjects with life expectancy ≥ 12 weeks

          5. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          6. Subjects with measurable or evaluable (measurable or non-measurable) lesions
             identified by RECIST version 1.1. (However, for phase II study, only subjects with
             measurable lesions can be allowed to enrolled.)

          7. Subjects with confirmed adequate hematologic, renal and liver function as follows:

               -  Absolute neutrophil count (ANC) ≥ 1.500/μL

               -  Platelet ≥ 100,000 μL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Serum creatinine ≤ 1.5 X ULN (but, subjects with CrCl or eGFR ≥60 mL/min many
                  participate)

               -  Serum calcium level ≤ 12 mg/dL

               -  Total bilirubin ≤ 1.5 X ULN (except for elevated total bilirubin due to Gilbert's
                  Syndrome)

               -  Liver function tests:

                    -  If there is no evidence of liver metastases: ALT and AST ≤ 2.5 x ULN

                    -  If liver metastases are documented: ALT and AST ≤ 5 x ULN

          8. Subjects who understand and are willing to comply with the protocol at the judgment of
             the investigator

          9. Subjects who voluntarily agree to participate in the study and sign the informed
             consent form

        Exclusion Criteria:

          1. Subjects expected to have hypersensitivity to active ingredient and any component of
             this investigational product

          2. Subjects who previously received drugs of taxane class (subjects who administratethe
             last dose of drug of taxane class ≥ 1 year ago as from the randomization day(C1D1) and
             have recurrence confirmed can be enrolled)

          3. Subjects receiving first-line chemotherapy for recurrent or metastatic breast cancer
             at the time of study during screening. However, the following subjects should be
             allowed to participate:

               -  Subjects who had the last administration of adjuvant or neoadjuvant therapy ≥ 1
                  year ago from randomization (C1D1) for prior breast cancer that is not recurrent
                  or metastatic, and its toxic symptoms have disappeared may participate.

               -  ER/PR(+) subjects that had second-line endocrine therapy may be enrolled. (also,
                  subjects who concomitantly used CDK4/6 inhibitors can be enrolled.)

          4. Subjects who received radiotherapy within 2 weeks from the randomization day (C1D1)
             (subjects who have completed local radiotherapy as palliative therapy for the purpose
             of pain relief for sites (eg, sites of bone metastasis, etc.) other than the target
             lesion and have recovered from the resulting acute toxicity (eg, bone marrow
             suppression) should be participate.)

          5. Subjects with confirmed heart failure of New York Heart Association (NYHA) class 2 or
             higher, or clinically significant arrhythmia uncontrolled by drug treatments, at the
             time of study entry

          6. Subjects with confirmed cardiovascular disease (including unstable angina pectoris,
             myocardial infarction, stroke, and transient ischemic attack) that occurred within 24
             weeks prior to study entry, which is deemed to be clinically significant by the
             investigator

          7. Subjects whose left ventricular ejection fraction (LVEF) measured by echocardiogram,
             MUGA scan, or standard procedures of study site is < lower limit of normal (50%, if
             the institutional lower limit of normal is not set) within 12 weeks prior to study
             entry

          8. Subjects with uncontrolled hypertension at the time of randomization (SBP > 140 mmHg
             or DBP > 90 mmHg despite drug treatments)

          9. Subjects with known active hepatitis B or C, or hepatobiliary disorders[however, the
             following subjects may participate:

               -  Subjects with Gilbert's Syndrome, asymptomatic gallstone, liver metastases, or
                  stable chronic liver disease may participate at the discretion of the
                  investigator.

               -  Carriers of hepatitis B or C virus may participate if they remain on antiviral
                  treatment [subjects with positive HCV ab are not considered as carriers of
                  hepatitis C virus if HCV RNA titer is negative])

         10. Known positive human immunodeficiency virus (HIV)

         11. Confirmed neuropathy grade ≥ 2 (based on CTCAE v4.03) at the time of study entry

         12. Subjects with confirmed uncontrolled intercurrent disease or condition including
             significant mental disease or social status which, in the investigator's judgment, may
             affect compliance with study procedures

         13. Subjects with a history of primary malignancy other than breast cancer. However, the
             subjects should be allowed to participate if:

               -  It has been at least 5 years or they are disease-free since completion of tumor
                  treatment

               -  It has been at least 1 year since complete resection of basal/squamous cell
                  cancer, radical resection of papillary thyroid cancer, or successful treatment of
                  carcinoma in situ of the cervix

         14. Subjects with central nervous system metastasis at the time of study entry (central
             nervous system metastasis should be confirmed through brain image in the
             investigator's judgment, if symptomatic.)

         15. Subjects expected to require bisphosphonate treatment at the time of study entry, or
             prophylactic use of bisphosphonate in the absence of bone related disease during the
             study, in the investigator's judgment (Subjects on bisphosphonate for bone metastasis
             or osteoporosis 2 weeks prior to the IP administration can be participate and are
             permitted for concomitant administration during the study.)

         16. Subjects determined inappropriate to orally administer the IP at the time of study
             participation based on the investigator's judgment

               -  Clinically significant or uncontrolled congenital or acquired gastrointestinal
                  disease

               -  Subjects with confirmed diseases that may interfere with the IP's administration,
                  transfer to digestive tract, or absorption including ileus and inflammatory bowel
                  disease (Crohn's disease and ulcerative colitis)

         17. Pregnant or breast-feeding women

         18. Subjects of childbearing potential who are unwilling to remain abstinent nor use
             adequate contraception during the study and at least 12 weeks after the end of
             treatment

         19. Subjects who received other IP or used an investigational device within 4 weeks prior
             to the administration of this IP

         20. Subjects who are unable to participate in the study at the discretion of investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:[Phase II] Objective Response Rate (ORR)
Time Frame:Participants will be followed every 6 weeks until progression, an expected average of 9 months.
Safety Issue:
Description:Objective Response Rate (ORR) is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (v.1.1) criteria.

Secondary Outcome Measures

Measure:[Phase II] Progression Free Survival (PFS)
Time Frame:From date of randomization, assessed up to 18 months.
Safety Issue:
Description:Progression Free Survival (PFS) is defined as the time from date of randomization until the date of first documented progression or death
Measure:[Phase III] Objective Response Rate (ORR)
Time Frame:Participants will be followed every 6 weeks until progression, an expected average of 9 months.
Safety Issue:
Description:Objective Response Rate (ORR) is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (v.1.1) criteria.
Measure:[Phase II&III] Overall Survival(OS)
Time Frame:Until 6 months after the last participant is enrolled, assessed minimum to 18 months.
Safety Issue:
Description:Overall survival(OS) is defined as the time from the date of inclusion to the date of death, regardless of the cause of death.
Measure:[Phase II&III] Time to Treatment Failure(TTF)
Time Frame:through study completion, an expected average of 4.5 year.
Safety Issue:
Description:TTF is defined as the time from the randomization date to the date of discontinuation of treatment, regardless of the cause.
Measure:[Phase II&III] Disease Control Rate(DCR)
Time Frame:through study completion, an expected average of 4.5 year.
Safety Issue:
Description:DCR is defined as the percentage of subjects who were evaluated for complete response(CR), partial response(PR), and stable disease(SD) as the best response among from randomization to End of treatment(EOT).
Measure:[Phase II&III] Quality of life(QoL)
Time Frame:C1D1, C2D1, C4D1, C7D1, C10D1 (each cycle is 28 days) and study completion, up to 18 months.
Safety Issue:
Description:To evaluate changes versus baseline using the EQ-5D.
Measure:Incidence of Treatment-Emergent Adverse Events [Safety]
Time Frame:Up to 28 days after last investigational product administraion.
Safety Issue:
Description:Number and Description of Adverse Events

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daehwa Pharmaceutical Co., Ltd.

Trial Keywords

  • Recurrent breast cancer
  • Metastatic breast cancer
  • MBC
  • Firstline chemotherapy
  • Paclitaxel
  • Liporaxel
  • Taxol

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