Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Menopause

Antineoplastic Agents

All Drugs and Chemicals

Vinorelbine

Hormones

Letrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Tubulin Modulators

Antimitotic Agents

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

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

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

Oral Vinorelbine

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

Aleix Prat, MD, PhD

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.

VENTANA is a phase 0 multicenter, window of opportunity, three-arm, randomized clinical trial of oral metronomic vinorelbine (VNB) and letrozole versus either treatment alone in postmenopausal women with newly diagnosed untreated HR+ and HER2-negative, stage I-III operable breast cancer. Other eligibility criteria include primary tumor size 1 cm (cT1-3) and N0-1, ECOG PS 0-1 and evaluable diagnostic tumor sample.

Primary objective is to test if Oral Metronomic Vinorelbine and Letrozole induce a superior anti-proliferative effect than either drug alone in patients with early breast cancer defined as Luminal by PAM50/HER2-negative. This will be evaluated by measuring the expression of 11 proliferative genes contained in the PAM50/Prosigna® array (BIRC5, CCNB1, CDC20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS and UBE2C), as surrogate biomarker of its anticancer activity. By evaluating other breast cancer-related gene signatures (560 genes), the antiangiogenic and immunogenic potential of treatment arms will be compared and other genes regulated in a treatment-specific manner identified. These analyses will be performed in different PAM50-defined subtypes (Luminal, LuminalA or LuminalB). Clinical efficacy and safety of treatments will also be evaluated.

Patients will first undergo screening and mandatory collection of core tumor biopsies for study analysis. Patients are randomized (1:1:1) to receive Letrozole 2.5mg daily, oral Vinorelbine 50mg 3 days a week or Letrozole 2.5mg daily and oral Vinorelbine 50mg 3 times a week. After 3 weeks of treatment, patients will undergo surgery, and both pre-treatment and post-treatment surgery samples will be analyzed. Alternatively, if surgery will be delayed, a tumor core biopsy will be collected. Anyway, post-treatment sample should be collected within 5 days after end of treatment in order to observe the biological response.

Axillar and mammary surgery will be done according to local standards; however, sentinel lymph node biopsy previous to surgery is not permitted. Following surgical excision, adjuvant treatment will be as per investigator´s choice and local standards of care outside the scope of this protocol. End of study is 28 days (±3 days) after last study drug dose with a safety follow-up visit.

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

Randomized, Open-label, Three-arm, Parallel, Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole Versus Letrozole or Vinorelbine Alone in Post-menopausal Women With Hormone Receptor-positive HER2-negative Early Breast Cancer

* 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.

* 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 3 treatment arms in the entire study population (evaluable patients defined as Luminal by IHC) and separately, in patients defined as either Luminal A or Luminal B by PAM50

Comparison of the 3 treatment arms in the entire PAM50-defined Luminal population (LuminalA+LuminalB) and separately, in the LuminalA or LuminalB subtypes.

* Expression data of breast cancer genes will be log base 2 transformed and normalized using 5 house-keeping genes
* Analysis will be performed in the entire PAM50-defined Luminal population (LuminalA+LuminalB) and separately, in the LuminalA or LuminalB subtypes.
* Aim of this outcome measure is to identify those genes with a significant difference between the VNB+Letrozole arms compared to the VNB or Letrozole monotherapy arms.

* Incidence and severity of Adverse Events (assessed by CTCAE v.4.03)
* Incidence of treatment interruptions due to toxicity

Spots Global Cancer Trial Database for proliferation signature