MEtronomic TrEatment Option in Advanced bReast cAncer (METEORA-II)
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|ClinicalTrials.gov Identifier: NCT02954055|
Recruitment Status : Active, not recruiting
First Posted : November 3, 2016
Last Update Posted : February 2, 2021
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Paclitaxel Drug: Cyclophosphamide Drug: Capecitabine Drug: Vinorelbine||Phase 2|
The prognosis for patients with locally advanced or metastatic disease (ABC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed BC patients present with ABC, and 30% to 50% of patients diagnosed at earlier stages will subsequently develop metastatic disease.
In the first-line treatment of HER2 (Human Epidermal Growth factor Receptor 2) negative ABC patients, various chemotherapy regimens can be used including taxanes, which are among the most active agents in BC. Single agent response rates range from 20 to 50%. However, eventually all patients will progress with a median time to progression of 5 to 7 months. A weekly (qw) over a three-weekly (q3w) administration schedule of paclitaxel has been shown to be more effective in the metastatic as well as in the adjuvant setting after standard chemotherapy
The VEX regimen was recently investigated within a phase II trial currently ongoing at the European Institute of Oncology (IEO) (IEO number IEOS582/111; EudraCT Number: 2010-024266-21; title: "A phase II study of metronomic oral chemotherapy with cyclophosphamide plus capecitabine and vinorelbine in metastatic breast cancer patients"). Patients received vinorelbine 40 mg orally on days 1, 3 and 5 every week, cyclophosphamide 50 mg daily and capecitabine 500 mg 3 times a day.
Given the promising activity of the VEX regimen in a pre-treated population of advanced breast cancer patients and the good tolerability, the aim of the present trial is to investigate whether the VEX schedule may improve efficacy and tolerability as compared to standard paclitaxel treatment in advanced or metastatic ER-positive/HER2-negative breast cancer patients.
The concept of the VEX metronomic treatment is to administer the combination for as long as the patient has the possibility of deriving a benefit from it. The time to treatment failure (TTF) has been chosen as primary endpoint for this trial. TTF is defined as time from the date of randomization to the date when the final dose of trial treatment is administered. Chemotherapy may need to be stopped due to lack of tolerability, lack of efficacy or patient preference through subjective symptom assessment. TTF is a composite endpoint combining all these feasibility aspects of a treatment. It is therefore uniquely suited to the research question of the current trial. The secondary endpoints progression-free survival, disease control and safety will allow further assessment of the feasibility of the VEX metronomic treatment versus the paclitaxel monotherapy regimen.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Trial of Metronomic Oral Vinorelbine Plus Cyclophosphamide and Capecitabine (VEX) Versus Weekly Paclitaxel as First-line or Second-line Treatment in Patients With ER-positive/HER2-negative Advanced or Metastatic Breast Cancer|
|Actual Study Start Date :||September 13, 2017|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||March 2022|
Active Comparator: Arm A
Paclitaxel 90 mg/m2 days 1, 8, 15 q4w. Patients will continue to receive assigned treatment until progression or lack of tolerability.
Other Name: Paclitaxel Sandoz
Experimental: Arm B
Cyclophosphamide 50 mg orally once daily continuously, Capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, Vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients will continue to receive assigned treatment until progression or lack of tolerability.
Other Name: Endoxan Baxter
Other Name: Xeloda
Other Name: Navelbine
- Time to treatment failure (TTF) compared between treatment groups. [ Time Frame: From date of randomization until the date the final dose of trial treatment was given due to documented progression, lack of tolerability or until further treatment is declined, assessed up to 36 months from enrollment of the first patient. ]Efficacy and tolerability, measured by time to treatment failure, of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) versus weekly paclitaxel, using an intent-to-treat analysis approach.
- Frequency of targeted adverse events (safety and tolerability). [ Time Frame: Time from day 1 of cycle 1 until 28 days after stopping trial treatment. ]Frequency of adverse events by type and worst grade experienced.
- Disease control [ Time Frame: From date of randomization until the date of first documented progression, assessed up to 36 months from enrollment of the first patient. ]Best overall response of complete response (CR) or partial response (PR), or stable disease (SD) lasting for at least 24 weeks, measured from randomisation to progression.
- Progression free survival (PFS) [ Time Frame: Time from randomization until documented disease progression, assessed up to 36 months from the enrollment of the first patient. ]Distribution of PFS for each treatment group using Kaplan-Meier; median PFS with two-sided 95% confidence interval (CI). PFS according to RECIST 1.1 criteria or death, whichever occurs first.
- Overall Survival [ Time Frame: From day 1 of cycle 1 until death from any cause (censored at date of last assessment of vital status for patients lost to follow up), assessed up to 36 months from the enrollment of the first patient. ]Overall survival from time of randomisation will be summarised for each treatment group.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02954055
|Study Chair:||Elisabetta Munzone, MD||European Institute of Oncology|