Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/Metastatic Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer

NCT03007992 | Completed Phase 2 DMC

• 1 other identifier: 2015-007
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the trial is to investigate the efficacy of metronomic treatment with daily oral vinorelbine in terms of clinical benefit rate based on local radiological assessment in patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; Vinorelbine; Metronomic chemotherapy

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  The primary endpoint is the determination of the Clinical Benefit Rate (CBR) at 24 weeks after start of treatment. The response to treatment is measured by computer tomography (CT) or magnetic resonance imaging (MRI) for measurable lesions and evaluation for non-measurable lesions at 24 weeks after start of treatment.

  24 weeks after start of treatment.

Secondary Outcomes (12)

• Overall response rate (ORR)

  6 months after last patient last treatment

• Disease control rate (DCR)

  6 months after last patient last treatment

• Duration of disease control (DoDC)

  6 months after last patient last treatment

• Duration of stable disease (DoSD)

  6 months after last patient last treatment

• Duration of response (DoR)

  6 months after last patient last treatment

Study Arms (1)

Vinorelbine Oral

EXPERIMENTAL

Test product: Navelbine® 20 mg / 30 mg soft capsules

Drug: Vinorelbine

Interventions

Vinorelbine DRUG

Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any adaptation to body weight or body surface area) without breaks. Treatment will continue until disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's decision to stop the treatment.

Also known as: Navelbine® soft capsules

Vinorelbine Oral

Eligibility Criteria

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

You may qualify if:

• Written (personally dated and signed) informed consent prior to the performance of any trial specific procedure
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and/or the follow-up schedule
• Female patient ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1, which the investigator assesses as being stable at time of screening
• Estimated life expectancy ≥ 16 weeks
• Histologically confirmed adenocarcinoma of the breast
• Documented locally advanced or metastatic disease, previously untreated by palliative chemotherapy and not amenable to any curative treatment
• Hormone receptor positive disease determined by ≥ 1% positive stained cells for oestrogen and/or progesterone receptor by immunohistochemistry on the primary tumour or on a metastatic site
• HER2-negative disease assessed by 0-1+ immuno-histochemistry (IHC) or 2+ IHC with negative fluorescence in situ hybridization (FISH) or CISH) on the primary tumour or on a metastatic site
• Availability of archival (from the most recently obtained sample) or fresh tumour tissue from patients included in the trial for the analysis of relevant metronomic biomarkers; one tumour block (preferred) or a minimum of 12 (recommended: 15) unstained slides to be provided
• Relapse ≤ 12 months from end of adjuvant hormonal therapy or pro¬gres¬sion during/after ≥ 1 line of endocrine therapy in the metastatic set¬ting and/or no longer candidate for further endocrine therapy
• Prior (neo-)adjuvant chemotherapy is allowed, if the interval between end of chemotherapy and date of registration is \> 12 months
• Prior treatment with everolimus and/or palbociclib in the frame of hormonal therapy is allowed
• Complete staging before registration (CT/MRI thorax and CT/MRI abdomen/pelvis ≤ 28 days before registration; bone scan ≤ 3 months before registration)
• Presence of ≥ 1 measurable lesion as per RECIST 1.1, which has not been previously irradiated

You may not qualify if:

• No recovery to ≤ Grade (G)1 side effects (exception: alopecia) of any prior anti-neoplastic treatment
• Aggressive locally advanced or metastatic breast cancer disease requiring systemic combination therapy
• Known or suspected central nervous system (CNS) and/or leptomeningeal involvement
• Current peripheral neuropathy ≥ G2
• Dysphagia or inability to swallow oral medication
• Malabsorption syndrome or disease significantly affecting GI-function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine
• Other serious illness or medical condition, such as but not limited to:
• Clinically significant cardiac disease or impaired cardiac function (such as: congestive heart failure requiring treatment (NYHA ≥ II); eft ventricular ejection fraction (LVEF) \< 50%; significant cardiac arrhythmia; atrial fibrillation; conduction abnormality such as congenital long QT syndrome or high grade/complete atrioventricular (AV)-blockage; acute coronary syndrome including myocardial infarction, unstable angina pectoris, coronary artery bypass graft, coronary angioplasty or stenting, if \< 3 months prior to registration; QTcF \> 480 msec at screening)
• Uncontrolled hypertension (\> 140/100 mmHg at rest (average of 3 consecutive readings))
• Unstable diabetes mellitus
• Uncontrolled hypercalcemia
• Clinically significant active infections (current or within the last 2 weeks prior to registration)
• Previous organ allograft
• Prior treatment with vinorelbine or other vinca alkaloids
• Concomitant endocrine therapy (e.g. tamoxifen, aromatase inhibitors, fulvestrant) for advanced breast cancer

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Pierre Fabre Pharma GmbH: collaborator

Study Sites (8)

Universitätsklinikum Düsseldorf, Frauenklinik

Düsseldorf, 40225, Germany

Location

Klinikum Frankfurt-Höchst Klinik für Gynäkologie und Geburtshilfe - Operative und konservative Gynäkologie, Gynäkologische Onkologie, Pränataldiagnostik, Geburtshilfe

Frankfurt am Main, 65929, Germany

Location

Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Gynäkologie

Halle, 06120, Germany

Location

Onkologische Schwerpunktpraxis Dr. Karcher, Dr. Fuxius, Dr. Debatin

Heidelberg, 69115, Germany

Location

Universitätsklinikum des Saarlandes, Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin

Homburg, 66421, Germany

Location

Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit

Mainz, 55131, Germany

Location

Klinikum der LMU München, Brustzentrum

München, 80377, Germany

Location

Schwerpunktpraxis für Hämatologie und Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Related Publications (1)

• Krajnak S, Decker T, Schollenberger L, Rose C, Ruckes C, Fehm T, Thomssen C, Harbeck N, Schmidt M. Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy: VinoMetro-AGO-B-046. J Cancer Res Clin Oncol. 2021 Nov;147(11):3391-3400. doi: 10.1007/s00432-021-03599-2. Epub 2021 Mar 20.

  PMID: 33743073 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Marcus Schmidt, Univ.-Prof. Dr. med.

  Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.-Prof. Dr. med.

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: January 2, 2017
• Study Start: December 1, 2016
• Primary Completion: March 2, 2019
• Study Completion: March 2, 2019
• Last Updated: August 12, 2019

Record last verified: 2019-02

Locations

DE (8)