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Breast CancerEarly Phase 1NCT02802748

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

A Early Phase 1 study testing Oral Vinorelbine and Letrozole in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 10 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Oral Vinorelbine and Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
10 sitesSpain
Study dates
Jul 2016to Jan 2018
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites
  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital de León

    León, 24071

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitari Sant Joan de Reus

    Reus, 43201

  • Clínica Quirón Sagrado Corazón

    Seville, 41013

  • Fundación Instituto Valenciano de Oncología

    Valencia, 46009

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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

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.

Read the detailed description

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.

Conditions
Breast Cancer
Being tested
Oral Vinorelbine, Letrozole
Keywords
Early Breast Cancer, Hormone Receptor-positive, Window-of-opportunity, PAM50, Luminal A, Luminal B, proliferation signature, metronomic vinorelbine, letrozole
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral VinorelbineDrug

    Also called Navelbine®

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

  • LetrozoleDrug

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

Study groups in NCT02802748
Study groupRoleWhat they receive
Metronomic Vinorelbine + LetrozoleExperimental* Oral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks * Letrozole: 2.5mg daily, for 3 weeks
Receives: Drug: Oral Vinorelbine; Drug: Letrozole
Letrozole aloneActive comparatorLetrozole: 2.5mg daily, for 3 weeks
Receives: Drug: Letrozole
Metronomic Vinorelbine aloneActive comparatorOral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks
Receives: Drug: Oral Vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At the time of surgery

Secondary outcomes (7)
  1. 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.

    • 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

    Measured: At the time of surgery

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

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

    Measured: At time of surgery

  3. Changes in the expression of angiogenic gene signature upon treatment

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

    Measured: At the time of surgery

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

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

    Measured: At time of surgery

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

    • 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.

    Measured: At the time of surgery

  6. Objective Response Rate (ORR) according to RECIST v1.1, assessed by ultrasound.

    Measured: Pre-surgery (3 weeks treatment)

  7. Safety profile

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

    Measured: Up to 7 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionJan 2018
  4. Study completionJan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02802748
Sponsor's protocol ID
SOLTI-1501
Other IDs
2015-004714-24, 2015
Status last verified
Sep 2018
First submitted
7 Jun 2016
Last updated
20 Sep 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31533777

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Oral Vinorelbine and Letrozole in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 10 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in the expression of the PAM50 proliferation signature upon treatment in patients defined as Luminal by PAM50 (time frame: At the time of surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02802748, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2018.

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