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A Open Study of Metronomic Oral Vinorelbine in Combination With Aromatase Inhibitors for the Treatment of Postmenopausal Women With Hormone Receptor Positive,HER2-negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease

NCT02730091

Description:

This study is designed to evaluate the clinical effects of the addition of metronomic oral vinorelbine to letrozole and anastrozole. The study will compare the efficacy and tolerability of oral metronomic vinorelbine administered in combination with letrozole or anastrozole, as treatment for hormone receptor-positive advanced or metastatic breast cancer without resistance to Aromatase Inhibitors (AI).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Open Study of Metronomic Oral Vinorelbine in Combination With Aromatase Inhibitors for the Treatment of Postmenopausal Women With Hormone Receptor Positive,HER2-negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
  • Official Title: A Randomized Open Study of Metronomic Oral Vinorelbine in Combination With Aromatase Inhibitors for the Treatment of Postmenopausal Women With Hormone Receptor Positive,HER2-negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease

Clinical Trial IDs

  • ORG STUDY ID: P/2015/253
  • NCT ID: NCT02730091

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleFEMARALetrozole or anastrozole
AnastrozoleARIMIDEXLetrozole or anastrozole
VinorelbineNavelbineVinorelbine + Anastrozole or letrozole

Purpose

This study is designed to evaluate the clinical effects of the addition of metronomic oral vinorelbine to letrozole and anastrozole. The study will compare the efficacy and tolerability of oral metronomic vinorelbine administered in combination with letrozole or anastrozole, as treatment for hormone receptor-positive advanced or metastatic breast cancer without resistance to Aromatase Inhibitors (AI).

Detailed Description

      Letrozole and Anastrozole are AI generally used as the first line of therapy for women with
      HR+ breast cancer.

      Furthermore, present hormonal treatments of advanced breast cancer (ABC) or Metastatic breast
      cancer (MBC) are sub-optimal, as only approximately one half of patients with oestrogen
      and/or progesterone receptor positive tumours will respond to therapy.

      For this patient population, chemotherapy is a valid option, especially after failure or
      intolerance to hormone therapy. Both combination and sequential single-agent chemotherapy are
      reasonable options. Based on the available data, sequential monotherapy is recommended as the
      preferred choice for MBC. Preferred first-line chemotherapy single agents are anthracyclines,
      taxanes, capecitabine, gemcitabine and vinorelbine.

      The development of oral chemotherapy formulations offer numerous benefits to patients,
      oncologists, oncology nurses, pharmacists and healthcare providers Metronomic therapy (MT)
      refers to repetitive, low doses of chemotherapy drugs. MT exerts an effect not only on tumor
      cells, but also on their microenvironment. In particular, the low-dose schedule compromises
      the repairing process of endothelial cells, leading to an anti-angiogenic effect. A
      systematic review of the results of phase I, II and III studies suggests that MT is a
      treatment option for breast cancer patients, has a low toxicity profile, efficacy in most
      patients and has potentially significant cost-effective advantages for public health.
    

Trial Arms

NameTypeDescriptionInterventions
Letrozole or anastrozoleActive ComparatorLetrozole 2,5 mg once a day or anastrozole 1 mg once a day until disease progression, unacceptable toxicity, patient's refusal, consent withdrawal, death, or discontinuation from the study treatment for any other reason.
  • Letrozole
  • Anastrozole
Vinorelbine + Anastrozole or letrozoleExperimentalOral vinorelbine 50 mg (1 soft capsule of 30 mg and 1 soft capsule of 20 mg) three times a week every ( Monday, Wednesday and Friday) before lunch and letrozole 2,5 mg once a day or anastrozole 1 mg once a day until disease progression, unacceptable toxicity, patient's refusal, consent withdrawal, death, or discontinuation from the study treatment for any other reason.
  • Letrozole
  • Anastrozole
  • Vinorelbine

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has signed informed consent before any trial related activities and according
             to local guidelines

          -  Women with advanced (inoperable loco regionally recurrent or metastatic) breast cancer

          -  No prior systemic anti-cancer therapy for advanced disease.

          -  Patient is postmenopausal. Postmenopausal status is defined either by:

               -  Prior bilateral oophorectomy

               -  Age > 60

               -  Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy,
                  tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal
                  range per local normal range

          -  Patient has a histological and/or cytological confirmed diagnosis of estrogen-receptor
             positive and/or progesterone receptor positive breast cancer by local laboratory (
             determined by >10% positive stained cells for estrogen receptor by IHC on the primary
             tumor or on metastatic site whichever the value of progesterone receptor).

          -  Patient has HER2-negative breast cancer defined as a negative in situ hybridization
             test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization
             (FISH, CISH, or SISH) test is required by local laboratory testing.

          -  Patient must have either:

               -  Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
                  criteria or,

               -  At least one lytic bone lesion or . Non measurable disease

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status <2

          -  Patient has adequate bone marrow and organ function as defined by the following
             laboratory values:

               -  Absolute neutrophil count ≥ 1.5 × 109/L

               -  Platelets ≥ 100 × 109/L

               -  Hemoglobin ≥ 8.0 g/dL

               -  Normal calcium (corrected for serum albumin)

               -  Serum creatinine should be below 2 x ULN

               -  In absence of liver metastases, alanine aminotransferase (ALT) and aspartate
                  aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver
                  metastases, ALT and AST should be < 5 × ULN.

               -  Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
                  within normal range of the central laboratory in patients with well documented
                  Gilbert's Syndrome

          -  Life expectancy > 16 weeks

        Exclusion Criteria:

          -  Patient who received vinorelbine in adjuvant setting.

          -  Patient with a known hypersensitivity to oral vinorelbine, létrozole, Anastrozole or
             any of the excipients or others vinca-alcaloïdes. 3. Patient who received any prior
             anti-cancer therapy (including chemotherapy) for advanced disease with the exception
             of surgery.

        Note:

        • Patients who received (neo) adjuvant therapy for breast cancer are eligible. Prior
        therapy with letrozole or anastrozole in the (neo) adjuvant setting is permitted if the
        disease free interval is greater than 24 months from the completion of treatment.

          -  Patient has a concurrent malignancy or malignancy within 5 years of randomization,
             with the exception of adequately treated, basal or squamous cell carcinoma,
             non-melanomatous skin cancer or curatively resected cervix cancer.

          -  Patient with known CNS metastases.

          -  Patient with impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection)

          -  Patient with a known history of HIV infection (testing not mandatory)

          -  Patient who any other concurrent severe and/or uncontrolled medical condition that
             would, in the investigator's judgment, contraindicate patient participation in the
             clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.)

          -  Patient with active cardiac disease or a history of cardiac dysfunction including any
             of the following:

        History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 6
        months prior to study entry History of documented congestive heart failure (New York Heart
        Association functional classification III-IV) Documented cardiomyopathy

          -  Patient with peripheral neuropathy>grade 2 CTCAE version 4.0

          -  Patient who had major surgery within 14 days prior to starting study drug or has not
             recovered from major side effects

          -  Patient who concurrently using other antineoplastic agents.

          -  Patient who has received radiotherapy for palliation ≤ 2 weeks prior to randomization,
             and who has not recovered to grade 1 or better from related side effects of such
             therapy (with the exception of alopecia) and/or from whom ≥ 30% of the bone marrow was
             irradiated.

          -  Participation in another clinical trial with any investigational drug within 30 days
             prior to randomization and/or during the study.

          -  Pregnancy or lactating patients

          -  Patient with history of surgical resection extended to the stomach or small intestine

          -  Patient with a severe infection current or recent (within 2 weeks)

          -  Patient needs long-term oxygen therapy

          -  Patient with rare hereditary problems of fructose intolerance

          -  In combination with the vaccine against yellow fever
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival (PFS)
Time Frame:up to 5 years
Safety Issue:
Description:Progression Free Survival is defined as the time from randomization until objective tumor progression or death from any cause if progression did not occur. Subjects will also be considered to have progressed if they have treatment discontinuation with documented evidence of clinical deterioration due to breast cancer. If a patient has not an event, PFS will be censored at the date of the last adequate tumor assessment.

Secondary Outcome Measures

Measure:health-related quality of life using HRQoL QLQ-C30 and BR23
Time Frame:up to 5 years
Safety Issue:
Description:using EORTC QLQ-C30 (targeted dimensions: Global Health, physical and Emotional Dimensions, Fatigue and pain) HRQoL will be considered as the first secondary endpoint in order to confirm clinical benefit for the patient since we need more follow up to observe an impact on overall survival (OS).
Measure:overall response rate (ORR)
Time Frame:up to 5 years
Safety Issue:
Description:ORR and as defined by RECIST 1.1.
Measure:clinical benefit rate (CBR)
Time Frame:up to 5 years
Safety Issue:
Description:CBR, defined as percentage of patients with complete response (CR), partial response (PR) per RECIST or stable disease (SD) lasting 24 weeks or longer
Measure:Safety assessed by NCI CTCAE version 4.0",
Time Frame:up to 5 years
Safety Issue:
Description:using NCI CTCAE version 4.0

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Centre Hospitalier Universitaire de Besancon

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