MEtronomic TrEatment Option in Advanced bReast cAncer

NCT02954055 | Completed Phase 2 Results DMC

• 2 other identifiers: IBCSG 54-162016-002200-39
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 20

Brief 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 conventional paclitaxel monotherapy.

Conditions

Breast Cancer

Keywords

locally advanced; metastatic; breast cancer; ER-positive; HER2-negative; Stage IV

Outcome Measures

Primary Outcomes (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.

  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)

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

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

• Disease Control

  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.

• Progression Free Survival (PFS)

  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.

• Overall Survival

  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.

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Paclitaxel 90 mg/m2 days 1, 8, 15 q4w. Patients will continue to receive assigned treatment until progression or lack of tolerability.

Drug: Paclitaxel

Arm B

EXPERIMENTAL

Metronomic 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.

Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Vinorelbine

Interventions

Paclitaxel DRUG

Arm A

Also known as: Paclitaxel Sandoz

Arm A

Cyclophosphamide DRUG

Arm B

Also known as: Endoxan Baxter

Arm B

Capecitabine DRUG

Arm B

Also known as: Xeloda

Arm B

Vinorelbine DRUG

Arm B

Also known as: Navelbine

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (20)

Centro di Riferimento Oncologico (CRO)

Aviano, Italy

Location

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

Bologna, 40138, Italy

Location

Ospedale di Bolzano Oncologia Medica Via lorenz Bohler 5

Bolzano, 39100, Italy

Location

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

Brescia, 25123, Italy

Location

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

Brindisi, 72100, Italy

Location

Candiolo Cancer Institute (FPO-IRCCS)

Candiolo, Italy

Location

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

Cremona, 26100, Italy

Location

Ospedale Misericordia di Grosseto

Grosseto, Italy

Location

ASST Ovest Milanese Oncology Department Via Papa Giovanni Paolo II

Legnano, Italy

Location

Ospedale Generale Provinciale di Macerata

Macerata, Italy

Location

IRST IRCCS Division of medical oncology Via Maroncelli 40

Meldola, 47014, Italy

Location

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

Milan, 20141, Italy

Location

Osp. Sacro Cuore Don Calabria Division in Medical Oncology

Negrar, Italy

Location

Istituti Clinici Scientifici Maugeri SpA SB

Pavia, Italy

Location

Ospedale S. Maria delle Croci

Ravenna, Italy

Location

Ospedale Infermi Uo Oncologia Via Settembrini 2

Rimini, 47923, Italy

Location

Fondazione Policlinico Universitario A.Gemelli

Rome, Italy

Location

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

Torino, 10126, Italy

Location

Asst Bg Ovest Ospedale Di Treviglio

Treviglio, Italy

Location

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

Varese, 21100, Italy

Location

Related Publications (8)

• 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.

  PMID: 19228622 BACKGROUND

• 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.

  PMID: 24126121 BACKGROUND

• 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.

  PMID: 16249346 BACKGROUND

• 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.

  PMID: 18160686 BACKGROUND

• 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.

  PMID: 20498403 BACKGROUND

• 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.

  PMID: 18375893 BACKGROUND

• 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.

  PMID: 18420499 BACKGROUND

• 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.

  PMID: 37440239 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Paclitaxel; Cyclophosphamide; Capecitabine; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Heidi Roschitzki, PhD
• Organization: ETOP IBCSG Partners Foundation

heidi.roschitzki@etop.ibcsg.org

+41 31 511 94 00

Study Officials

• Elisabetta Munzone, MD

  European Institute of Oncology

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: November 3, 2016
• Study Start: September 13, 2017
• Primary Completion: November 17, 2021
• Study Completion: November 23, 2022
• Last Updated: February 26, 2024
• Results First Posted: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (20)