NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT05569811
- Lead Sponsor
- SOLTI Breast Cancer Research Group
- Brief Summary
VALENTINE is a parallel, non-comparative, three-arm, randomized 1:2:2 open-label, multicenter, exploratory study in women or men with primary operable HR+/HER2-negative breast cancer with ki67 ≥ 20% and/or high genomic risk (defined by gene signature) aiming at evaluating the clinical benefit and biological effects of HER3-DXd with/without letrozole as a neoadjuvant treatment regimen.
The primary aim is to evaluate the ability of each treatment strategy to achieve a pCR at surgery. This study is exploratory and no formal comparison between treatment arms is intended. The inclusion of a chemotherapy treatment arm serves as an internal response control instead of using historical data as comparators. In addition, the chemotherapy control arm is the standard of care appropriate treatment in these patients, to include this arm will ensure the recruitment of the target patient population (patients should have indication for neoadjuvant chemotherapy) and allowing comparison of secondary endpoint such as safety and/or HrQoL.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CHEMOTHERAPY Chemotherapy - HER3-DXd Patritumab deruxtecan - HER3-DXd + Endocrine therapy (ET) Patritumab deruxtecan - HER3-DXd + Endocrine therapy (ET) Letrozole -
- Primary Outcome Measures
Name Time Method Rate of pCRBL (ypT0/is ypN0) at surgery before treatment and surgery complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination.
- Secondary Outcome Measures
Name Time Method pCRB (pathological complete response in the breast) before treatment and surgery defined as the complete absence of invasive carcinoma in the breast on histological examination after treatment, irrespective of in situ carcinoma in the breast.
Tumor overall objective response rate (ORR) before treatment and pre-surgery defined as the proportion of subjects with a Partial Responses (PR) or a Complete Responses (CR) according to RECIST v1.1 as per Investigator's assessments by breast MRI
HER3 receptor expression and ERBB3 mRNA expression level from baseline to C2D1 HER3 receptor expression levels by IHC and ERBB3 mRNA expression level by gene expression.
Proliferation from baseline to C2D1 changes in ki67 IHC
Quality of Life assessed by EORTC QLQ-C30 changes from baseline until 30 days after the surgery visit European Organization for Research and Treatment of Cancer's (EORTC) core quality of life questionnaire (EORTC QLQ-C30, version 3.0). EORTC QLQ-C30 is used to measure QoL within the preceding 7 days. The EORTC QLQ-C30 is a questionnaire consisting of 30 items where each item is scored using a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much).
Quality of Life assessed by EORTC-BR45 changes from baseline until 30 days after the surgery visit European Organization for Research and Treatment of Cancer's (EORTC) core quality for assessing quality of life in breast cancer patients (EORTC-BR45). QLQ-BR45 is used to measure HRQoL within the preceding 7 days or 28 days depending on the items. The EORTC QLQ-BR45 is a questionnaire consisting of 45 items where each item is scored using a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much).
iDFS rate 3 years follow-up and 5 years follow-up iDFS defined as the time from randomization to any of the following events:
* Ipsilateral invasive breast tumor recurrence (IIBTR): invasive breast cancer involving the same breast parenchyma as the original primary.
* Regional invasive breast cancer recurrence: Invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast.
* Distant recurrence: Metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer.
* Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause.
* Contralateral invasive breast cancer.
* Second primary non-breast invasive cancer.
* Progression during neoadjuvant treatment.CelTIL score changes from baseline to C2D1 CelTIL score (CelTIL = = -0.8 × tumor cellularity (in %) + 1.3 × TILs (in %)
Rate of Residual cancer burden (RCB) category status (0, I, II, III) before treatment and surgery assessed by a local pathologist at surgery according to the MD Anderson Cancer Center recommendations.
Number of Participants with Adverse events (safety) from randomization/enrollment to end of safety follow up assessed up to approximately 30 days after the surgery visit Type, incidence, severity (as graded by the NCI CTCAE v. 5.0), seriousness and attribution to the study medications of TEAEs, AESI and any laboratory abnormalities.
Trial Locations
- Locations (25)
Complejo Hospitalario San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital Universitario de Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
Hospital Universitario de Canarias
🇪🇸Tenerife, Islas Canarias, Spain
Hospital Universitari Vall d' Hebrón
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital General de Catalunya
🇪🇸Barcelona, Spain
HAU de Manresa
🇪🇸Manresa, Spain
HU Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario de Badajoz
🇪🇸Badajoz, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Comp. Hosp.Univ. Santiago (Chus)
🇪🇸Santiago De Compostela, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital de Basurto
🇪🇸Bilbao, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Son Espases
🇪🇸Palma De Mallorca, Spain
H La Fe
🇪🇸Valencia, Spain
Hospital Sant Joan de Reus
🇪🇸Reus, Spain
H.Univ. Arnau de Vilanova de Lleida
🇪🇸Lleida, Spain
Hospital Clínico de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Rey Juan Carlos
🇪🇸Móstoles, Madrid, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, La Coruña, Spain
ICO Badalona
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Puerta de Hierro de Majadahonda
🇪🇸Madrid, Spain