Clinical Trials /

Metronomic Oral Chemotherapy With Cyclophosphamide, Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients

NCT04304352

Description:

This is a phase II study assessing the activity and safety of metronomic chemotherapy with cyclophosphamide and capecitabine and vinorelbine in advanced breast cancer patient in four different cohort of patients: 1. Untreated (naïve) patients with endocrine responsive disease 2. Pretreated patients with endocrine responsive disease 3. Untreated (naïve) patients with triple negative disease 4. Pretreated patients with triple negative disease The primary endpoint will be the progression-free survival

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Metronomic Oral Chemotherapy With Cyclophosphamide, Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients
  • Official Title: A Phase II Study of Metronomic Oral Chemotherapy With Cyclophosphamide Plus Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: IEO S582/111 RE324/2
  • NCT ID: NCT04304352

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
VinorelbineMetronomic VinorelbineMetronomic VEX
CapecitabineMetronomic CapecitabineMetronomic VEX
CyclophosphamideMetronomic CyclophosphamideMetronomic VEX

Purpose

This is a phase II study assessing the activity and safety of metronomic chemotherapy with cyclophosphamide and capecitabine and vinorelbine in advanced breast cancer patient in four different cohort of patients: 1. Untreated (naïve) patients with endocrine responsive disease 2. Pretreated patients with endocrine responsive disease 3. Untreated (naïve) patients with triple negative disease 4. Pretreated patients with triple negative disease The primary endpoint will be the progression-free survival

Detailed Description

      This is an institutional, monocentric, open-label, phase II study of oral "metronomic"
      Vinorelbine plus Capecitabine and Cyclophosphamide (VEX) in patients with advanced breast
      cancer .

      Patients will receive the combination regimen as follow:

      Cyclophosphamide 50 mg daily Capecitabine 500 mg, thrice daily Vinorelbine 40 mg orally
      thrice a week

      Four independent cohorts of patients will be evaluated in the study:

        1. Untreated (naïve) patients with endocrine responsive disease

        2. Pretreated patients with endocrine responsive disease

        3. Untreated (naïve) patients with triple negative disease

        4. Pretreated patients with triple negative disease Combination will be administered until
           disease progression or unacceptable toxicity.

      The primary endpoint will be to assess the Time to progression (TTP) of VEX combination in
      the four different cohorts
    

Trial Arms

NameTypeDescriptionInterventions
Metronomic VEXExperimentalMetronomic VEX (Oral Cyclophosphamide 50 mg daily continuous, Oral Capecitabine 500 mg, thrice daily continuous, Oral Vinorelbine 40 mg day 1,3 and 5 every week
  • Vinorelbine
  • Capecitabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Pre- or post-menopausal women (age ≥18 years) with histologically or cytologically
             (cell block) proven, locally advanced (inoperable) or metastatic breast carcinoma.
             Immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PgR),
             human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor
             (EGFR) according to European Institute of Oncology guidelines is mandatory.

          2. Patients with HER2 overexpressed tumors, are eligible if they had received previous
             trastuzumab therapy for advanced disease, and/or a treatment with anti HER2 targeted
             therapy.

          3. Patients fulfilling one of the following criteria:

               -  Patients with measurable disease as per RECIST 1.1 criteria. This is defined as
                  at least one lesion that can be accurately measured in at least one dimension
                  (longest diameter to be recorded) as 20 mm with conventional techniques or as 10
                  mm with spiral CT scan

               -  Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of
                  measurable disease as defined by RECIST 1.1 criteria. Bone lesions must be
                  evaluable by plain CT or MRI. Patients with lesions identified only on
                  radionucleotide bone scan are not eligible.

          4. Patients may have received any primary and/or adjuvant therapies, as any previous
             lines of chemotherapy and endocrine therapy for advanced disease. Patients may have
             received metronomic capecitabine, methotrexate and cyclophosphamide in adjuvant
             setting at least 12 months before study entry

          5. Previous treatment with capecitabine, cyclophosphamide and vinorelbine not in
             metronomic schedule for advanced disease is allowed, provided that the patient has
             progressive disease at study entry and the patients should not be defined as
             "refractory" to treatments (Pathological Response or Complete Response or Stable
             Disease > 6 months).

          6. Patients may have had previous hormonal therapy as treatment of metastatic disease
             provided that the patient has progressive disease at study entry. Hormonal therapy
             must be discontinued prior to study entry, excluding Luteinizing Hormone-Releasing
             Hormone (LHRH) analogue.

          7. Life expectancy greater than 6 months.

          8. Eastern Cooperative Oncology Group (ECOG) Performance Status performance status <2

          9. Patients must have normal organ and marrow function as defined below:

               -  leukocytes ≥ 3,000/μL

               -  absolute neutrophil count ≥ 1,000/μL

               -  platelets ≥ 100,000/μL

               -  Haemoglobin ≥ 10 g/dl

               -  total bilirubin within normal institutional limits

               -  Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 2 X
                  institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥ 60 mL/min/1.73 m for patients with creatinine levels above
                  institutional normal

         10. Geographically accessible for follow up.

         11. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Previous metronomic chemotherapy for advanced disease with capecitabine,
             cyclophosphamide and vinorelbine

          2. Patients defined as "refractory" to capecitabine, cyclophosphamide and vinorelbine
             (Progression Disease or Stable Disease < 6 months).

          3. Presence of symptomatic cerebral or leptomeningeal involvement.

          4. Previous or concomitant other malignancy except basal or squamous cell carcinoma of
             the skin or adequately treated in situ carcinoma of the cervix.

          5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          6. Malabsorption syndrome or disease affecting significantly gastrointestinal function or
             major resection of the stomach or proximal small bowel that could affect absorption of
             oral vinorelbine

          7. Concurrent treatment with any other anti-cancer therapy except LHRH analogue.

          8. Patients with pre-existing motor or sensory peripheral neuropathy grade 2 according to
             NCI criteria
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to progression (TTP)
Time Frame:28 days
Safety Issue:
Description:the time between the first study dose administration and the date of progression of the disease or cancer-related death, whichever occurs first

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Institute of Oncology

Last Updated

April 24, 2020