Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial
Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-02-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359231225032 |
| _version_ | 1797307109426069504 |
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| author | Wen-Jia Zuo Li Chen Yu Shen Zhong-Hua Wang Guang-Yu Liu Ke-Da Yu Gen-Hong Di Jiong Wu Jun-Jie Li Zhi-Ming Shao |
| author_facet | Wen-Jia Zuo Li Chen Yu Shen Zhong-Hua Wang Guang-Yu Liu Ke-Da Yu Gen-Hong Di Jiong Wu Jun-Jie Li Zhi-Ming Shao |
| author_sort | Wen-Jia Zuo |
| collection | DOAJ |
| description | Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 ). |
| first_indexed | 2024-03-08T00:52:33Z |
| format | Article |
| id | doaj.art-0d7935c7ecb74a46860ea61e0ae9fa69 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-03-08T00:52:33Z |
| publishDate | 2024-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-0d7935c7ecb74a46860ea61e0ae9fa692024-02-14T19:03:54ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592024-02-011610.1177/17588359231225032Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trialWen-Jia ZuoLi ChenYu ShenZhong-Hua WangGuang-Yu LiuKe-Da YuGen-Hong DiJiong WuJun-Jie LiZhi-Ming ShaoBackground: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 ).https://doi.org/10.1177/17588359231225032 |
| spellingShingle | Wen-Jia Zuo Li Chen Yu Shen Zhong-Hua Wang Guang-Yu Liu Ke-Da Yu Gen-Hong Di Jiong Wu Jun-Jie Li Zhi-Ming Shao Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial Therapeutic Advances in Medical Oncology |
| title | Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial |
| title_full | Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial |
| title_fullStr | Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial |
| title_full_unstemmed | Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial |
| title_short | Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial |
| title_sort | rational and trial design of fascinate n a prospective randomized precision based umbrella trial |
| url | https://doi.org/10.1177/17588359231225032 |
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