Clinical Trials /

A Study to Evaluate the Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension in Triple Negative Breast Cancer Patients

NCT03671044

Description:

The Nanosomal Docetaxel Lipid Suspension (NDLS) consists of uniformly sized micro particles of docetaxel suspended in a lipid based formulation. The advantage of such a Lipid Based formulation of Docetaxel is an improvement of the safety profile by eliminating excipients, polysorbate 80 and ethanol which are present in conventional Docetaxel formulations (Taxotere®). This randomized, open-label study is designed to assess the efficacy and safety of Nanosomal Docetaxel Lipid Suspension at the dose of 75 mg/m2 and at the dose of 100 mg/m2 compared to Taxotere® at the dose of 100 mg/m2 in triple-negative breast cancer patients with Locally Advanced or Metastatic Breast Cancer. Patients will continue the treatment in the absence of disease progression and unacceptable toxicity. Disease status and tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines. 657 patients (219 patients per arm) will be randomized in the study. The trial will be conducted as per the ICH GCP Guidelines E6 (R1), Schedule Y (Amended Version 2013), Declaration of Helsinki (Fortaleza, Brazil, October 2013), ICMR Guidelines for Biomedical Research on Human subjects and in accordance with other applicable guidelines.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension in Triple Negative Breast Cancer Patients
  • Official Title: A Global, Multicenter, Three Arms, Open-label Randomized Study to Evaluate the Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension Compared to Taxotere® (Docetaxel Injection Concentrate) in Triple-negative Breast Cancer Patients With Locally Advanced or Metastatic Breast Cancer After Failure to Prior Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 0063-17
  • NCT ID: NCT03671044

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Nanosomal Docetaxel Lipid Suspension (75 mg/m2)Nanosomal Docetaxel Lipid Suspension - 75 mg/m2
Nanosomal Docetaxel Lipid Suspension (100 mg/m2)T2, Nanosomal Docetaxel Lipid Suspension (100 mg/m2)
Taxotere® (100 mg/m2)R, Taxotere® (100 mg/m2)

Purpose

The Nanosomal Docetaxel Lipid Suspension (NDLS) consists of uniformly sized micro particles of docetaxel suspended in a lipid based formulation. The advantage of such a Lipid Based formulation of Docetaxel is an improvement of the safety profile by eliminating excipients, polysorbate 80 and ethanol which are present in conventional Docetaxel formulations (Taxotere®). This randomized, open-label study is designed to assess the efficacy and safety of Nanosomal Docetaxel Lipid Suspension at the dose of 75 mg/m2 and at the dose of 100 mg/m2 compared to Taxotere® at the dose of 100 mg/m2 in triple-negative breast cancer patients with Locally Advanced or Metastatic Breast Cancer. Patients will continue the treatment in the absence of disease progression and unacceptable toxicity. Disease status and tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines. 657 patients (219 patients per arm) will be randomized in the study. The trial will be conducted as per the ICH GCP Guidelines E6 (R1), Schedule Y (Amended Version 2013), Declaration of Helsinki (Fortaleza, Brazil, October 2013), ICMR Guidelines for Biomedical Research on Human subjects and in accordance with other applicable guidelines.

Detailed Description

      Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semi
      synthesis beginning with a precursor extracted from the renewable needle biomass of yew
      plants. It acts by disrupting the microtubular network in cells that is essential for mitotic
      and interphase cellular functions. The Nanosomal Docetaxel Lipid Suspension (NDLS) consists
      of uniformly sized micro particles of docetaxel suspended in a lipid based formulation.
      Docetaxel Lipid Suspension for Injection 20 mg/80 mg was approved for marketing in India.
      Intas Pharmaceuticals Ltd., is marketing this drug in India under the Brand name of
      DOCEAQUALIP 20/80 (Nanosomal Docetaxel Lipid Suspension for Injection 20/80 mg/vial) since
      2013. This randomized, open label study is designed to assess the efficacy and safety of
      Nanosomal Docetaxel Lipid Suspension at the dose of 75 mg/m2 and at the dose of 100 mg/m2
      compared to reference product, Taxotere® at a dose of 100 mg/m2 in triple-negative breast
      cancer patients with Locally Advanced or Metastatic Breast Cancer. 657 patients (219 patients
      per arm) will be randomized in the study.

      To ensure consistent interpretation of measurable disease and objective endpoints for the
      study, all imaging studies performed throughout the study will be sent to an independent
      Central Radiological Facility for tumor measurement and evaluation of response. This
      independent review will have no impact on patient care. Continued participation in the study
      will be determined by assessment of clinical and radiological response by the Principal
      Investigator, and/or Radiologist. Efficacy evaluation will be done by CT scan/MRI and Bone
      scan at the end of treatment cycle 3 and will continue at every 3 cycles while the patient
      remains on treatment and compared to base line. Patient will continue study treatment until
      unacceptable toxicity or progression of disease. Patient will be screened up to 14 days prior
      to dosing and will be dosed on day 1. Patient will be advised to come in the facility at
      least 02 hours prior to dosing and will remain in the clinical facility until the completion
      of study drug administration. Dosing of patients will be done on ambulatory basis; hence
      patient hospitalization is optional. It is the responsibility of the PI to ensure that
      adequate medical supervision and care is available for the study patients during housing and
      entire duration of the study for utmost safety and wellbeing of the study patients. All
      safety analyses will be performed on the Safety set. Safety variables include AEs, clinical
      laboratory parameters, vital signs, physical examinations and electrocardiogram etc. Safety
      variables will be listed and summarized with descriptive statistics, as appropriate.
    

Trial Arms

NameTypeDescriptionInterventions
Nanosomal Docetaxel Lipid Suspension - 75 mg/m2ExperimentalExperimental: NDLS for Injection, 75 mg/ m2 Nanosomal Docetaxel Lipid Suspension for Injection; Dose: 75 mg/m2; Frequency: Every 3-weeks; Duration of treatment: Patient will be dosed with drug until disease progression and/or unacceptable toxicity
  • Nanosomal Docetaxel Lipid Suspension (75 mg/m2)
T2, Nanosomal Docetaxel Lipid Suspension (100 mg/m2)ExperimentalExperimental: NDLS for Injection, 100 mg/ m2 Nanosomal Docetaxel Lipid Suspension for Injection; Dose: 100 mg/m2; Frequency: Every 3-weeks; Duration of treatment: Patient will be dosed with drug until disease progression and/or unacceptable toxicity
  • Nanosomal Docetaxel Lipid Suspension (100 mg/m2)
R, Taxotere® (100 mg/m2)Active ComparatorActive Comparator: Taxotere® Injection Concentrate Docetaxel Injection Concentrate; Dose: 100 mg/m2; Frequency: Every 3-weeks; Duration of treatment: Patient will be dosed with drug until disease progression and/or unacceptable toxicity
  • Taxotere® (100 mg/m2)

Eligibility Criteria

        Inclusion Criteria:

          1. The patient willing to give written signed and dated informed consent to participate
             in the study.

          2. Patient must have histopathologically or cytologically confirmed triple negative
             breast cancer.

          3. Patients may have received one prior chemotherapy regimen for adjuvant therapy and/or
             one chemotherapy treatment/regimen for firstline metastatic therapy

          4. Patients with locally advanced or metastatic breast cancer after failure of prior
             chemotherapy.

          5. Have at least one measurable lesion as per the RECIST criteria (version 1.1).

          6. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to two

          7. Left Ventricular Ejection fraction (LVEF) greater than or equal to 50 percentage as
             per Echocardiography (ECHO).

          8. Patient must have recovered from any toxic effects of previous chemotherapy or
             radiotherapy as judged by the Investigator.

          9. Previous chemotherapy or radiotherapy should be completed 4 weeks prior to start of
             IMP administration.

         10. Patients with life expectancy of at least 6 months.

         11. Serum pregnancy test at screening and urine pregnancy test on Day 1 (before
             randomization) must be negative.

         12. Sexually active women, unless surgically sterile or postmenopausal for at least 12
             consecutive months, must use an effective method of avoiding pregnancy (including
             oral, transdermal, or implanted contraceptives [any hormonal method in conjunction
             with a secondary method], intrauterine device, female condom with spermicide,
             diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide
             by sexual partner or sterile [at least 6 months prior to Study drug administration]
             sexual partner) for at least four weeks prior to study drug administration, during
             study and up to 30 days after the last dose of study drug. Cessation of birth control
             after this point should be discussed with a responsible physician.

         13. Patient with adequate bone marrow, renal and hepatic function.

        Exclusion Criteria:

          1. Patient who has a history of hypersensitivity reactions to Docetaxel or any other
             component of formulation or to any drugs formulated with polysorbate 80.

          2. Patients with a history of HER2 positive over expression and hormone receptor positive
             (ER or PR)

          3. Patient who is already exposed to Docetaxel injection in metastatic setting.

          4. Any of the cardiac conditions like Unstable angina, Myocardial infarction within the
             past six months, Severe uncontrolled ventricular arrhythmias, Clinically significant
             pericardial disease, Electrocardiographic evidence of acute ischemia, Patient with
             evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block)
             except in whom the disease has been stable for the past six months, History of cardiac
             disease that met the NYHA Classification class 2 or greater

          5. Uncontrolled diabetes or infection.

          6. Known history of drug addiction within last one year.

          7. Patients with known CNS lesions (brain metastasis or carcinomatous meningitis) except
             for asymptomatic brain metastases.

          8. The receipt of an investigational medicinal product or participation in other drug
             research study within a period of 30 days prior to the first dose of investigational
             medicinal Product for the current study.

          9. Pre-existing motor or sensory neurotoxicity of a severity greater than or equal to
             grade two as defined by NCI CTCAE 4.03 criteria.

         10. Known case of HIV infection.

         11. Any other condition that, in the investigator's judgment, might increase the risk to
             the patient or decrease the chance of obtaining satisfactory data needed to achieve
             the objectives of the study.

         12. Patients who are unwilling or unable to follow protocol requirements
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of the patients with Objective Response Rate (i.e., CR + PR) as the Best Overall Response Rate (i.e., CR + PR) in the test arm (NDLS) compared to reference arm (Taxotere)
Time Frame:Approximately 2 years after study initiation
Safety Issue:
Description:Non-inferiority of NDLS (75 mg/m2, 100 mg/m2) compared to Taxotere (100 mg/m2)

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Approximately 2 years after study initiation
Safety Issue:
Description:PFS will be evaluated from the date of first dosing to the date of tumor progression (as per the RECIST 1.1 Criteria) or death (due to any cause) whichever occurred first
Measure:To evaluate the overall survival (OS) of the patients
Time Frame:Approximately 2 years after study initiation
Safety Issue:
Description:OS will be evaluated from the date of first dosing to the date of tumor progression (as per the RECIST 1.1 Criteria) or death (due to any cause) whichever occurred first
Measure:Incidence of adverse events as assessed by clinical examination, and/or laboratory parameters
Time Frame:Approximately 2 years after study initiation
Safety Issue:
Description:adverse events as assessed by CTCAE v4.0

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jina Pharmaceuticals Inc.

Trial Keywords

  • Triple Negative Breast Cancer
  • Docetaxel

Last Updated

July 28, 2020