Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Prostatic Neoplasms

Head and Neck Neoplasms

Uterine Cervical Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Vinorelbine

Immunomodulating Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Patients presenting advanced refractory breast cancer

Patients presenting advanced refractory head and neck cancer

Patients presenting advanced refractory cervix cancer

Patients presenting advanced refractory prostate cancer

Patients presenting advanced refractory solid tumour with high mutational load

Patient will be treated by metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy

Durvalumab + Tremelimumab + metronomic Vinorelbine

This is a phase I/II national, multicentre, multiple cohort, prospective open-label, non-randomised and non-comparative study, to evaluate the safety and activity of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy for the treatment of advanced solid tumours.

Methodology:

The study divided in two parts:

* Phase I part: dose escalation study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy,
* Phase II part: activity study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy.

Indication:

Patient eligible to the study are patients with histologically confirmed locally advanced or metastatic solid tumours, resistant to conventional therapies, and candidate to experimental therapy by local clinical board, from the following primary tumours: head and neck, prostate, cervix, and breast cancers, as well as miscellaneous malignancies with high mutational load.

This is a phase I/II national, multicentre, multiple cohort, prospective open-label, non-randomised and non-comparative study divided in two parts:

* Phase I part: dose escalation study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy,
* Phase II part: activity study of metronomic oral vinorelbine associated with durvalumab + tremelimumab combination immunotherapy.

Metronomic Oral Vinorelbine Plus Anti-PD-L1/Anti-CTLA4 ImmunothErapy in Patients With Advanced Solid Tumours

A Phase I/II Basket Trial Evaluating a Combination of Metronomic Oral Vinorelbine Plus Anti-PD-L1/Anti-CTLA4 ImmunothErapy in Patients With Advanced Solid Tumour

National Cancer Institute, France

AstraZeneca

Pierre Fabre Laboratories

UNICANCER

Breast Diseases

Skin Diseases

Menopause

Hormones

Letrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

* 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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Metronomic Oral Vinorelbine Plus Anti-PD-L1/Anti-CTLA4 ImmunothErapy in Patients With Advanced Solid Tumours	NCT03518606	Advanced Solid ... Breast Cancer Head and Neck C... Cervix Cancer Prostate Cancer	Durvalumab + Tr...	18 Years -	UNICANCER
Metronomic Oral Vinorelbine Plus Anti-PD-L1/Anti-CTLA4 ImmunothErapy in Patients With Advanced Solid Tumours	NCT03518606	Advanced Solid ... Breast Cancer Head and Neck C... Cervix Cancer Prostate Cancer	Durvalumab + Tr...	18 Years -	UNICANCER
Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole in HR+/HER2-negative Early Breast Cancer Patients (VENTANA)	NCT02802748	Breast Cancer	Oral Vinorelbin... Letrozole	18 Years -	SOLTI Breast Cancer Research Group

Spots Global Cancer Trial Database for metronomic vinorelbine