A Open Study of Metronomic Oral Vinorelbine in Combination With Aromatase Inhibitors for the Treatment of Postmenopausal Women With Hormone Receptor Positive,HER2-negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease

NCT02730091 | Terminated Phase 3 DMC

• 1 other identifier: P/2015/253
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the clinical effects of the addition of metronomic oral vinorelbine to letrozole and anastrozole. The study will compare the efficacy and tolerability of oral metronomic vinorelbine administered in combination with letrozole or anastrozole, as treatment for hormone receptor-positive advanced or metastatic breast cancer without resistance to Aromatase Inhibitors (AI).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  Progression Free Survival is defined as the time from randomization until objective tumor progression or death from any cause if progression did not occur. Subjects will also be considered to have progressed if they have treatment discontinuation with documented evidence of clinical deterioration due to breast cancer. If a patient has not an event, PFS will be censored at the date of the last adequate tumor assessment.

  up to 5 years

Secondary Outcomes (4)

• health-related quality of life using HRQoL QLQ-C30 and BR23

  up to 5 years

• overall response rate (ORR)

  up to 5 years

• clinical benefit rate (CBR)

  up to 5 years

• Safety assessed by NCI CTCAE version 4.0",

  up to 5 years

Study Arms (2)

Letrozole or anastrozole

ACTIVE COMPARATOR

Letrozole 2,5 mg once a day or anastrozole 1 mg once a day until disease progression, unacceptable toxicity, patient's refusal, consent withdrawal, death, or discontinuation from the study treatment for any other reason.

Drug: Letrozole; Drug: Anastrozole

Vinorelbine + Anastrozole or letrozole

EXPERIMENTAL

Oral vinorelbine 50 mg (1 soft capsule of 30 mg and 1 soft capsule of 20 mg) three times a week every ( Monday, Wednesday and Friday) before lunch and letrozole 2,5 mg once a day or anastrozole 1 mg once a day until disease progression, unacceptable toxicity, patient's refusal, consent withdrawal, death, or discontinuation from the study treatment for any other reason.

Drug: Letrozole; Drug: Anastrozole; Drug: Vinorelbine

Interventions

Letrozole DRUG

Letrozole 2.5 mg daily

Also known as: FEMARA

Letrozole or anastrozole; Vinorelbine + Anastrozole or letrozole

Anastrozole DRUG

anastrozole 1 mg daily

Also known as: ARIMIDEX

Letrozole or anastrozole; Vinorelbine + Anastrozole or letrozole

Vinorelbine DRUG

50 mg three times a week (Monday Wednesday and Friday)

Also known as: Navelbine

Vinorelbine + Anastrozole or letrozole

Eligibility Criteria

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

You may qualify if:

• Patient has signed informed consent before any trial related activities and according to local guidelines
• Women with advanced (inoperable loco regionally recurrent or metastatic) breast cancer
• No prior systemic anti-cancer therapy for advanced disease.
• Patient is postmenopausal. Postmenopausal status is defined either by:
• Prior bilateral oophorectomy
• Age \> 60
• Age \<60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range
• Patient has a histological and/or cytological confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory ( determined by \>10% positive stained cells for estrogen receptor by IHC on the primary tumor or on metastatic site whichever the value of progesterone receptor).
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
• Patient must have either:
• Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or,
• At least one lytic bone lesion or . Non measurable disease
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status \<2
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 × 109/L

You may not qualify if:

• Patient who received vinorelbine in adjuvant setting.
• Patient with a known hypersensitivity to oral vinorelbine, létrozole, Anastrozole or any of the excipients or others vinca-alcaloïdes. 3. Patient who received any prior anti-cancer therapy (including chemotherapy) for advanced disease with the exception of surgery.
• Note:
• Patients who received (neo) adjuvant therapy for breast cancer are eligible. Prior therapy with letrozole or anastrozole in the (neo) adjuvant setting is permitted if the disease free interval is greater than 24 months from the completion of treatment.
• Patient has a concurrent malignancy or malignancy within 5 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervix cancer.
• Patient with known CNS metastases.
• Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient with a known history of HIV infection (testing not mandatory)
• Patient who any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.)
• Patient with active cardiac disease or a history of cardiac dysfunction including any of the following:
• History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry History of documented congestive heart failure (New York Heart Association functional classification III-IV) Documented cardiomyopathy
• Patient with peripheral neuropathy\>grade 2 CTCAE version 4.0
• Patient who had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
• Patient who concurrently using other antineoplastic agents.
• Patient who has received radiotherapy for palliation ≤ 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 30% of the bone marrow was irradiated.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Pierre Fabre Medicament: collaborator

Study Sites (1)

CHU Besançon

Besançon, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Anastrozole; Vinorelbine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Erion DOBI

  Centre Hospitalier Universitaire de Besancon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: April 6, 2016
• Study Start: February 24, 2016
• Primary Completion: March 23, 2020
• Study Completion: March 23, 2020
• Last Updated: February 1, 2021

Record last verified: 2021-01

Locations

FR (1)