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

NCT ID: NCT04304352

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-29
• Study Completion Date: 2023-12-31

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:

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

Conditions

Advanced Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metronomic VEX

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

Group Type: EXPERIMENTAL

Vinorelbine

Intervention Type: DRUG

Metronomic Vinorelbine 40 mg orally thrice a week

Capecitabine

Intervention Type: DRUG

Metronomic Capecitabine 500 mg, thrice daily

Cyclophosphamide

Intervention Type: DRUG

Metronomic Cyclophosphamide 50 mg daily

Interventions

Vinorelbine

Metronomic Vinorelbine 40 mg orally thrice a week

Intervention Type: DRUG

Capecitabine

Metronomic Capecitabine 500 mg, thrice daily

Intervention Type: DRUG

Cyclophosphamide

Metronomic Cyclophosphamide 50 mg daily

Intervention Type: DRUG

Other Intervention Names

Metronomic Vinorelbine; Metronomic Capecitabine; Metronomic 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Colleoni, MD

Role: PRINCIPAL_INVESTIGATOR

European Institute of Oncology

Locations

European Institute of Oncology

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Emilia Montagna, MD

Role: CONTACT

emilia.montagna@ieo.it

+390257489243

Claudia A Sangalli

Role: CONTACT

claudia.sangalli@ieo.it

+390257489840

Facility Contacts

Emilia Montagna, MD

Role: primary

emilia.montagna@ieo.it

+390257489 ext. 243

Other Identifiers

IEO S582/111 RE324/2

Identifier Type: -

Identifier Source: org_study_id