Metronomic Oral Chemotherapy With Cyclophosphamide, Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients (VEX)
Primary Purpose
Advanced Breast Cancer
Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Vinorelbine
Capecitabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
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.
- 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
- 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).
- 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.
- Life expectancy greater than 6 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status performance status <2
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
- Geographically accessible for follow up.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Previous metronomic chemotherapy for advanced disease with capecitabine, cyclophosphamide and vinorelbine
- Patients defined as "refractory" to capecitabine, cyclophosphamide and vinorelbine (Progression Disease or Stable Disease < 6 months).
- Presence of symptomatic cerebral or leptomeningeal involvement.
- Previous or concomitant other malignancy except basal or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.
- 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.
- 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
- Concurrent treatment with any other anti-cancer therapy except LHRH analogue.
- Patients with pre-existing motor or sensory peripheral neuropathy grade 2 according to NCI criteria
Sites / Locations
- European Institute of OncologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metronomic VEX
Arm Description
Metronomic 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
Outcomes
Primary Outcome Measures
Time to progression (TTP)
the time between the first study dose administration and the date of progression of the disease or cancer-related death, whichever occurs first
Secondary Outcome Measures
Full Information
NCT ID
NCT04304352
First Posted
March 9, 2020
Last Updated
June 27, 2023
Sponsor
European Institute of Oncology
1. Study Identification
Unique Protocol Identification Number
NCT04304352
Brief Title
Metronomic Oral Chemotherapy With Cyclophosphamide, Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients
Acronym
VEX
Official Title
A Phase II Study of Metronomic Oral Chemotherapy With Cyclophosphamide Plus Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2011 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Institute of Oncology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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:
Untreated (naïve) patients with endocrine responsive disease
Pretreated patients with endocrine responsive disease
Untreated (naïve) patients with triple negative disease
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:
Untreated (naïve) patients with endocrine responsive disease
Pretreated patients with endocrine responsive disease
Untreated (naïve) patients with triple negative disease
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
162 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metronomic VEX
Arm Type
Experimental
Arm Description
Metronomic 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
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Other Intervention Name(s)
Metronomic Vinorelbine
Intervention Description
Metronomic Vinorelbine 40 mg orally thrice a week
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Metronomic Capecitabine
Intervention Description
Metronomic Capecitabine 500 mg, thrice daily
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Metronomic Cyclophosphamide
Intervention Description
Metronomic Cyclophosphamide 50 mg daily
Primary Outcome Measure Information:
Title
Time to progression (TTP)
Description
the time between the first study dose administration and the date of progression of the disease or cancer-related death, whichever occurs first
Time Frame
28 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
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.
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
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).
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.
Life expectancy greater than 6 months.
Eastern Cooperative Oncology Group (ECOG) Performance Status performance status <2
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
Geographically accessible for follow up.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Previous metronomic chemotherapy for advanced disease with capecitabine, cyclophosphamide and vinorelbine
Patients defined as "refractory" to capecitabine, cyclophosphamide and vinorelbine (Progression Disease or Stable Disease < 6 months).
Presence of symptomatic cerebral or leptomeningeal involvement.
Previous or concomitant other malignancy except basal or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.
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.
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
Concurrent treatment with any other anti-cancer therapy except LHRH analogue.
Patients with pre-existing motor or sensory peripheral neuropathy grade 2 according to NCI criteria
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emilia Montagna, MD
Phone
+390257489243
Email
emilia.montagna@ieo.it
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia A Sangalli
Phone
+390257489840
Email
claudia.sangalli@ieo.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco Colleoni, MD
Organizational Affiliation
European Institute of Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
European Institute of Oncology
City
Milan
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilia Montagna, MD
Phone
+390257489
Ext
243
Email
emilia.montagna@ieo.it
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Metronomic Oral Chemotherapy With Cyclophosphamide, Capecitabine and Vinorelbine in Metastatic Breast Cancer Patients
We'll reach out to this number within 24 hrs