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Breast CancerPhase 2METEORA-IINCT02954055

MEtronomic TrEatment Option in Advanced bReast cAncer

A Phase 2 study testing Paclitaxel, Cyclophosphamide and Capecitabine in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 20 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi-center, randomized phase II trial that will randomise women with ER-positive, HER2-negative (Human Epidermal Growth factor Receptor 2-negative) metastatic or locally relapsed breast cancer in a ratio of 1:1 to receive a metronomic regimen of vinorelbine plus cyclophosphamide and capecitabine, or the… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Paclitaxel, Cyclophosphamide and Capecitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
20 sitesItaly
Study dates
13 Sep 2017to 23 Nov 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed HER2-negative locally advanced or metastatic (stage IV) breast cancer.
  • Maximum of one prior line of chemotherapy for advanced or metastatic breast cancer.
  • Measurable or non-measurable, but radiologically evaluable (except for skin lesions), disease according to RECIST 1.1 criteria.
  • Female aged 18 years or older.
  • Life expectancy > 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Show all 20Show fewer
  • ER-positive disease by local laboratory, determined on most recent available tissue (latest biopsy of metastatic lesion, otherwise prior biopsy or surgical specimen).
  • If previously treated with a taxane in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).
  • Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.
  • Normal hematologic status,
  • Absolute neutrophil count ≥1000/mm3 (1.0 × 109/L),
  • Platelets ≥ 100 × 109/L,
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
  • Normal renal function: serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula.
  • Normal liver function:
  • Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 3 × ULN) is allowed.
  • Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
  • Women of child bearing potential must have documented negative pregnancy test within 2 weeks prior to randomization and agree to acceptable birth control (non-hormonal) during and up to 6 months after trial therapy.
  • Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to starting screening procedures and randomization.
  • The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.

Who cannot join

  • More than one prior line of chemotherapy for advanced or metastatic breast cancer
  • Previous treatment for advanced or metastatic disease with taxanes, or capecitabine or vinorelbine or oral cyclophosphamide.
  • More than 2 lines of previous endocrine therapy for locally advanced or metastatic breast cancer.
  • Known active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of Central Nervous System (CNS) metastases or spinal cord compression are eligible if they are clinically and radiologically stable for at least 4 weeks before first dose of trial treatment and have not required high-dose steroid treatment in the last 4 weeks).
  • Peripheral neuropathy grade 2 or higher (CTCAE version 4.0).
  • Significant uncontrolled cardiac disease (i.e. unstable angina, myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.
Show all 11Show fewer
  • Pregnant or lactating.
  • Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).
  • Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.
  • Contraindications or known hypersensitivity to the trial medication or excipients.
  • The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Italy20 sites

  • Centro di Riferimento Oncologico (CRO)

    Aviano

  • A.O.U. di Bologna Policlinico S. Orsola-Malpighi Viale Ercolani 4/2

    Bologna, 40138

  • Ospedale di Bolzano Oncologia Medica Via lorenz Bohler 5

    Bolzano, 39100

  • Aziendale Spedali Civili di Brescia SSVD Breast Unit P.le Spedali Civili 1

    Brescia, 25123

  • "Antonio Perrino" Division of Medical Oncology Strada Statale 7 APPIA

    Brindisi, 72100

  • Candiolo Cancer Institute (FPO-IRCCS)

    Candiolo

  • ASST Di Cremona, Unità di Patologia Mammaria-Breast Unit VIALE CONCORDIA 1

    Cremona, 26100

  • Ospedale Misericordia di Grosseto

    Grosseto

  • ASST Ovest Milanese Oncology Department Via Papa Giovanni Paolo II

    Legnano

  • IRST IRCCS Division of medical oncology Via Maroncelli 40

    Meldola, 47014

  • Istituto Europeo di Oncologia, Division of Medical Senology, Via Ripamonti 435

    Milan, 20141

  • Osp. Sacro Cuore Don Calabria Division in Medical Oncology

    Negrar

  • Istituti Clinici Scientifici Maugeri SpA SB

    Pavia

  • Ospedale Generale Provinciale di Macerata

    Province of Macerata

  • Ospedale S. Maria delle Croci

    Ravenna

  • Ospedale Infermi Uo Oncologia Via Settembrini 2

    Rimini, 47923

  • Fondazione Policlinico Universitario A.Gemelli

    Rome

  • A.O.U Città della Salute e della Scienza di Torino SSCVD Oncologia Medica Senologica (Oncology Dep.- Breast Unit) Via Cherasco 23

    Torino, 10126

  • Asst Bg Ovest Ospedale Di Treviglio

    Treviglio

  • ASST Settelaghi - Ospedale di Circolo e Fondazione Macchi U.O Oncologia Medica Viale L. Borri, 57

    Varese, 21100

Other trials in Italy

About this study

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

This is a multi-center, randomized phase II trial that will randomise women with ER-positive, HER2-negative (Human Epidermal Growth factor Receptor 2-negative) metastatic or locally relapsed breast cancer in a ratio of 1:1 to receive a metronomic regimen of vinorelbine plus cyclophosphamide and capecitabine, or the conventional paclitaxel monotherapy.

Read the detailed description

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.

Conditions
Breast Cancer
Keywords
locally advanced, metastatic, breast cancer, ER-positive, HER2-negative, Stage IV
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02954055
Study groupRoleWhat they receive
Arm AActive comparatorPaclitaxel 90 mg/m2 days 1, 8, 15 q4w. Patients will continue to receive assigned treatment until progression or lack of tolerability.
Receives: Drug: Paclitaxel
Arm BExperimentalMetronomic VEX: 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.
Receives: Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Treatment Failure (TTF) Compared Between Treatment Groups.

    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.

    Measured: Assessed at the start of every 4-week (28-day) treatment cycle from randomization to the end of treatment date or discontinuation; median follow-up was 29 months, with a minimum of 0.2 months and maximum of 48.5 months.

Secondary outcomes (4)

  1. Frequency of Targeted Adverse Events (Safety and Tolerability).

    Frequency of adverse events by type and worst grade experienced.

    Measured: Time from day 1 of cycle 1 until 28 days after stopping trial treatment.

  2. Disease Control

    Defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD in the case of non-measurable disease only) lasting for at least 24 weeks (at least 2 scans), measured from randomization until first documentation of progressive disease. Best overall response was defined as best response recorded from randomization across all time points until disease progression. Confirmation of partial or complete response by an additional scan was not requested in this trial. Disease response and progression were assessed according to the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

    Measured: Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months.

  3. Progression Free Survival (PFS)

    PFS was defined as time from randomization until documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria or death, whichever occurred first; the death must have occurred within an interval of time corresponding to the interval of tumor re-evaluations. For patients without progression, follow-up was censored at the date of last disease assessment.

    Measured: Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months.

  4. Overall Survival

    Overall survival from time of randomisation will be summarised for each treatment group.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2016 (estimated)
  2. Study start13 Sep 2017
  3. Primary completion17 Nov 2021
  4. Study completion23 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02954055
Sponsor's protocol ID
IBCSG 54-16
Other IDs
2016-002200-39, 2016
Acronym
METEORA-II
Status last verified
Feb 2024
First submitted
26 Sep 2016
Last updated
26 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009 Feb 19;360(8):790-800. doi: 10.1056/NEJMra0801289. No abstract available.

    PubMed 19228622

  • Senkus E, Cardoso F, Pagani O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev. 2014 Mar;40(2):220-8. doi: 10.1016/j.ctrv.2013.09.015. Epub 2013 Oct 1.

    PubMed 24126121

  • Eniu A, Palmieri FM, Perez EA. Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer. Oncologist. 2005 Oct;10(9):665-85. doi: 10.1634/theoncologist.10-9-665.

    PubMed 16249346

  • Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. doi: 10.1056/NEJMoa072113.

    PubMed 18160686

  • Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. doi: 10.1200/JCO.2008.21.6457. Epub 2010 May 24.

    PubMed 20498403

  • Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699.

    PubMed 18375893

  • Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. doi: 10.1056/NEJMoa0707056.

    PubMed 18420499

  • Munzone E, Regan MM, Cinieri S, Montagna E, Orlando L, Shi R, Campadelli E, Gianni L, Palleschi M, Petrelli F, Bengala C, Generali D, Collova E, Puglisi F, Cretella E, Zamagni C, Chini C, Ruepp B, Loi S, Colleoni M; International Breast Cancer Study Group (IBCSG). Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: Final Results From the Phase 2 METEORA-II Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1267-1272. doi: 10.1001/jamaoncol.2023.2150.

    PubMed 37440239

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paclitaxel, Cyclophosphamide and Capecitabine in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Treatment Failure (TTF) Compared Between Treatment Groups. (time frame: Assessed at the start of every 4-week (28-day) treatment cycle from randomization to the end of treatment date or discontinuation; median follow-up was 29 months, with a minimum of 0.2 months and maximum of 48.5 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02954055, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.

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