Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole in HR+/HER2-negative Early Breast Cancer Patients (VENTANA)

NCT02802748 | Completed Early Phase 1

• 2 other identifiers: SOLTI-15012015-004714-24
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

VENTANA is a "window-of-opportunity" trial that will explore whether, similar to CDK4/6 inhibitors, Oral Metronomic Vinorelbine in combination with Letrozole induces a superior anti-proliferative effect than Letrozole alone.

Conditions

Breast Cancer

Keywords

Early Breast Cancer; Hormone Receptor-positive; Window-of-opportunity; PAM50; Luminal A; Luminal B; proliferation signature; metronomic vinorelbine; letrozole

Outcome Measures

Primary Outcomes (1)

• Changes in the expression of the PAM50 proliferation signature upon treatment in patients defined as Luminal by PAM50

  * Outcome measure determined by following formula: Mean suppression of proliferation signature score = 100 - \[geometric mean (post treatment proliferation score/pre-treatment proliferation score · 100)\]. * Comparison of the Oral Metronomic Vinorelbine (VNB)+Letrozole arms versus VNB or Letrozole monotherapy arms in patients defined as Luminal by PAM50.

  At the time of surgery

Secondary Outcomes (7)

• Changes in the expression of the PAM50 proliferation signature upon treatment in patients defined as Luminal by IHC and separately, in patients defined as either Luminal A or Luminal B by PAM50.

  At the time of surgery

• Changes in % of Ki67-positive cells (per IHC) upon treatment

  At time of surgery

• Changes in the expression of angiogenic gene signature upon treatment

  At the time of surgery

• Changes in the expression of immune-response-related gene signature upon treatment

  At time of surgery

• Changes in the expression of breast cancer related genes (contained in a 560 gene Custom CodeSet) upon treatment

  At the time of surgery

Study Arms (3)

Metronomic Vinorelbine + Letrozole

EXPERIMENTAL

* Oral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks * Letrozole: 2.5mg daily, for 3 weeks

Drug: Oral Vinorelbine; Drug: Letrozole

Letrozole alone

ACTIVE COMPARATOR

Letrozole: 2.5mg daily, for 3 weeks

Drug: Letrozole

Metronomic Vinorelbine alone

ACTIVE COMPARATOR

Oral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks

Drug: Oral Vinorelbine

Interventions

Oral Vinorelbine DRUG

Metronomic Schedule of Vinorelbine administered orally in a schedule monday-wednesday-friday, tuesday-thursday-saturday, etc

Also known as: Navelbine®

Metronomic Vinorelbine + Letrozole; Metronomic Vinorelbine alone

Letrozole DRUG

Letrozole will be administered orally at 2.5 mg QD for 3 weeks.

Letrozole alone; Metronomic Vinorelbine + Letrozole

Eligibility Criteria

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

You may qualify if:

• Written informed consent for all study procedures in accordance with local regulatory requirements before protocol-specific procedures are started.
• Postmenopausal status
• Histologically confirmed invasive breast carcinoma, with all of the following characteristics: Primary tumor greater than or equal to (\>/=) 1cm in largest diameter (cT1-3) and N0-Stage I to operable Stage III breast cancer
• Scheduled or possibility of scheduling primary surgery within study window (surgery or biopsy within 5 days after treatment completion)
• HR-positive breast cancer defined as ≥1% of anti-ER and/or anti-PgR stained tumor cells by IHC (per local assessment)
• HER2-negative BC by IHC (score 0 or 1+) and/or FISH/CISH/SISH (defined as a ratio of HER2/CEP17\<2 or single-probe average HER2 copy number \<4 signals/cell), as per local assessment.
• Known percentage of Ki67-positive tumor cells within pre-treatment sample or possibility of local assessment.
• Available pre-treatment core or possibility to take a new biopsy with enough tumor sample for study analysis
• ECOG performance status of 0 or 1
• Adequate organ function, determined by laboratory tests performed within 7 days before treatment start

You may not qualify if:

• Patients with cT4 or cN2-3 stage breast tumors
• Bilateral invasive, multicentric or metastatic breast cancer
• Patients with prior excisional biopsy of primary tumor and/or of axillar lymph nodes or or sentinel lymph node biopsy
• Patients for whom upfront chemotherapy is clinically judged appropriate as optimal neoadjuvant treatment
• Patients requiring imminent surgical procedure
• Any prior treatment for breast cancer except for patients with Lobular Carcinoma In Situ (LCIS) treated with surgery or with Ductal Carcinoma In Situ (DCIS) treated exclusively with mastectomy. In both cases, surgery must have taken place \>5 years prior diagnosis of current breast cancer
• Other concurrent secondary malignancies, except for appropriately treated non-melanoma skin carcinoma, in situ melanoma and/or in situ cervical/colon cancer
• Treatment with any investigational medicinal product or participation in another therapeutic clinical trial concurrently or in the 28 days prior randomization
• Current uncontrolled severe systemic disease that could interfere with the intended therapy (e.g. clinical significant cardiovascular disease, pulmonary or metabolic disease, wound healing disorders, severe infection, heart failure, ischemic heart disease)
• Hereditary fructose intolerance
• Major surgical procedure or significant traumatic lesion within 28 days prior to treatment allocation or anticipated need for major surgery during the course of the study treatment, except if related with the breast cancer
• Any psychological, family, sociological or geographical circumstance that could potentially represent an obstacle to compliance with the study protocol and the follow-up schedule; these circumstances will be discussed with the patient before enrolment in the trial

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Pierre Fabre Laboratories: collaborator

Study Sites (10)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de León

León, 24071, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, 43201, Spain

Location

Clínica Quirón Sagrado Corazón

Seville, 41013, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Adamo B, Bellet M, Pare L, Pascual T, Vidal M, Perez Fidalgo JA, Blanch S, Martinez N, Murillo L, Gomez-Pardo P, Lopez-Gonzalez A, Amillano K, Canes J, Galvan P, Gonzalez-Farre B, Gonzalez X, Villagrasa P, Ciruelos E, Prat A. Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial. Breast Cancer Res. 2019 Sep 18;21(1):108. doi: 10.1186/s13058-019-1195-z.

  PMID: 31533777 DERIVED

Related Links

• SOLTI Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine; Letrozole

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; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Aleix Prat, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 16, 2016
• Study Start: July 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: September 20, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)