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Phase 1a/1b Trial of Exercise Treatment in Hormone Receptor-Positive Metastatic Breast Cancer

激素受体阳性转移性乳腺癌运动治疗 1a/1b 期试验

基本信息

批准号：
10377322
负责人：
Neil Mukund Iyengar
金额：
$ 66.48万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-03 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377322
关键词：
Address Adherence Adverse event Aerobic Exercise Animals Antiestrogen Therapy Biological Breast Cancer Patient CDK4 gene Cancer Intervention Chronic Clinical Clinical Trials Common Terminology Criteria for Adverse Events Data Development Dose Emulsions Enrollment Exercise Exercise Test Exercise Therapy Fatigue Grant Image Imaging Techniques Malignant Neoplasms Measures Metastatic breast cancer Molecular Observational Study Oncology Outcome Pain Pathway interactions Patient-Focused Outcomes Patients Performance Status Pharmacology Phase Phase Ia Trial Phase Ia/Ib Trial Pilot Projects Plasma Polymerase Chain Reaction Postmenopause Prediction of Response to Therapy Prognosis Progression-Free Survivals Quality of life Randomized Controlled Trials Regimen Reporting Research Research Design Resistance Safety Signal Transduction Solid Structure Supervision Symptoms Techniques Technology Testing Time Toxic effect Tumor Burden Walking Woman Work anti-cancer antitumor effect appropriate dose base breast cancer progression cancer therapy circulating DNA clinical subtypes cohort cost drug development exercise capacity exercise prescription exercise training hormone receptor-positive hormone therapy improved improved outcome inhibitor innovation instrument liquid biopsy malignant breast neoplasm mouse model mutant novel phase III trial pre-clinical preclinical study primary endpoint public health relevance radiological imaging response safety and feasibility secondary endpoint standard of care therapy resistant treadmill treatment strategy tumor tumor DNA virtual

项目摘要

PROJECT SUMMARY/ABSTRACT Nearly half of patients receiving first line therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) do not respond to treatment, and virtually all develop treatment resistance. Efficacious but low cost strategies that can be chronically administered with minimal toxicity are urgently required. Structured aerobic exercise therapy (hereafter exercise) is one such candidate approach. However, most exercise-oncology studies to date have been conducted in early-stage cancers to test the impact of exercise on symptom control outcomes (e.g., fatigue, pain). To develop exercise as an anticancer strategy, early phase studies are required to determine the appropriate exercise dose for further testing – this is a mandatory prerequisite in drug development but one largely ignored in the development of exercise as a treatment strategy. The overall objective of this grant is to identify the optimal dose of exercise in patients with HR-positive MBC. Prior observational and preclinical evidence provide promising hypothesis-generating data of an association between exercise and improved prognosis. The next step in the development of exercise as an anti-cancer intervention is to identify the optimal dose for testing in randomized control trials (RCTs). Our group recently reported a vanguard clinical trial (R21 CA133186) showing, for the first time, the feasibility, safety, and promising benefit of a conservative exercise prescription in MBC patients with good performance status receiving 1st or 2nd-line therapy. Based on this strong scientific rationale, our specific aims are (1) to identify the maximum feasible dose (MFD) of exercise in a phase 1a dose-finding study, and (2) to further assess tolerability and biological / clinical activity in a phase 1b dose-expansion cohort. In Aim 1, 40 postmenopausal women receiving first-line therapy for HR-positive MBC will be allocated to one of five exercise doses which will consist of supervised individualized treadmill walking 3 to 5 days/week, at 50% to 85% exercise capacity for landmark 24 weeks. In Aim 2, 40 postmenopausal MBC patients will receive the MFD of exercise or one dose level below the MFD. The primary endpoint is tolerability. Secondary endpoints are biological and clinical activity. Biological activity will be assessed by change in tumor burden, quantified by circulating tumor DNA (ctDNA) in serially obtained liquid biopsies. Clinical activity will be assessed by radiographic tumor response, progression free survival, and quality of life measures. We hypothesize that a tolerable dose of exercise will be identified and that this dose will have antitumor activity characterized by reductions in tumor burden (ctDNA) and improvements in clinical response compared to historical data. This contribution is significant because it will inform the recommended phase 2 dose of exercise for testing in definitive RCTs. This proposal is innovative because it adapts rigorous standards from oncology drug development and incorporates novel liquid biopsy technology (e.g., ctDNA), thereby setting a new standard for exercise oncology research and practice.

项目总结/文摘