Phase I/II study to determine the safety and efficacy of Ribociclib in combination with hormone therapy and hypofractionated radiotherapy in breast cancer, with positive hormone receptors and negative HER2 status, in newly diagnosed, not immediately operable (or wishing to avoid surgery), elderly patient
概览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 85
- 试验地点
- 2
- 主要终点
- • Phase 1 For this purpose (primary end-point), the frequencies of the toxicity limiting doses will be determined during the 8 weeks of radiotherapy concomitant with the Ribociclib and hormone therapy and during the 3 months of post-radiotherapy follow-up. Toxicities are considered to be limiting if they are leading to discontinuation of treatment (cf dose adaptation in paragraph 6.4.1). The toxicities will be evaluated according to the CTCAE V4.03 scale.
概览
简要总结
• Phase 1: The main objective for the Phase I is to determine the Maximal Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) of Ribociclib in combination with hormone therapy and hypofractionated radiotherapy in elderly population. • Phase 2 : The main objective for the Phase II is to evaluate the efficacy of Ribociclib in association with hormone therapy and hypofractionated radiotherapy in elderly population.
入排标准
- 年龄范围
- 65 years 至 65+ years（65+ Years）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient registered in the study-screening phase;
- •Must be able to swallow ribociclib;
- •Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures
- •Must be willing to remain at the clinical site as required by the protocol.
- •Patient receiving, during the screening phase, 3 cycles of Ribociclib at 600mg without dose decreased;
- •Have a performance status of 0 to 2 on the ECOG Performance Scale;
- •Not immediately operable (stage of disease, comorbidities or refusal of surgery) with tumor in place;
- •Measurable disease based on RECIST 1.1;
- •Demonstrate adequate organ functions: Hemoglobin > 9 g/dL; Absolute neutrophil count > 1.5 G/L; Platelets > 100 G/L; etc...
- •Standard 12-lead ECG values defined as the mean of the triplicate ECGs • QTcF interval at screening < 450 msec (QT interval using Fridericia’s correction) • Mean resting heart rate 50-90 bpm (determined from the ECG)Indication of treatment with hormone therapy and hypofractioned radiotherapy;
排除标准
- •Patient eligible to resection surgery after 3 cycles of Ribociclib;
- •Patient eligible to neoadjuvant chemotherapy;
- •Concomitant bilateral breast cancer;
- •Known additional malignancy. Exceptions include basal cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy;
- •Contraindication for hormone therapy, Ribobociblib or radiotherapy;
- •Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
- •Severe dementia;
- •Patients unable to express their consent;
- •Vulnerable persons as defined by article L1121-5 - 8: a. Pregnant women, women in labor or breast-feeding mothers, persons deprived of their freedom by judicial or administrative decision, persons hospitalized without their consent by virtue of articles L. 3212-1 and L. 3213-1 and who are not subject to the provisions of article L. 1121-8; b. Persons admitted to a social or health facility for reasons other than research; c. Adults subject to a legal protection order or unable to give their consent.
结局指标
主要结局
• Phase 1 For this purpose (primary end-point), the frequencies of the toxicity limiting doses will be determined during the 8 weeks of radiotherapy concomitant with the Ribociclib and hormone therapy and during the 3 months of post-radiotherapy follow-up. Toxicities are considered to be limiting if they are leading to discontinuation of treatment (cf dose adaptation in paragraph 6.4.1). The toxicities will be evaluated according to the CTCAE V4.03 scale.
• Phase 1 For this purpose (primary end-point), the frequencies of the toxicity limiting doses will be determined during the 8 weeks of radiotherapy concomitant with the Ribociclib and hormone therapy and during the 3 months of post-radiotherapy follow-up. Toxicities are considered to be limiting if they are leading to discontinuation of treatment (cf dose adaptation in paragraph 6.4.1). The toxicities will be evaluated according to the CTCAE V4.03 scale.
• Phase 2:The primary endpoint will be the rate of non-progression at 24-months, defined as the percentage of patients who are alive and have not progressed 24 months after the completion of the Ribociclib and Radiotherapy concomitant phase. The objective response rate will be defined as the sum of complete response and partial response 24 months after the end of the Ribociclib and Radiotherapy concomitant phase divided by the number of evaluable patients.
• Phase 2:The primary endpoint will be the rate of non-progression at 24-months, defined as the percentage of patients who are alive and have not progressed 24 months after the completion of the Ribociclib and Radiotherapy concomitant phase. The objective response rate will be defined as the sum of complete response and partial response 24 months after the end of the Ribociclib and Radiotherapy concomitant phase divided by the number of evaluable patients.
次要结局
- The overall tolerance of Ribociclib during the patient’s length of participation will be evaluated using clinical and biological assessment and graded according to the CTCAE V4.03 scale.
- The overall survival at 24 and 60 months after the end of Ribociclib and Radiotherapy concomitant phase is defined as the time from the inclusion to death whatever the causes. Patients alive or lost at time of analysis will be censored at the date of the last known contact.
- The progression free survival at 24 and 60 months after the Ribociclib and Radiotherapy concomitant phase is defined as the time from the inclusion to progression, or death due to any cause whatever occurred first.
- The quality of life will be assessed with QLQ-C30, ELD14, and visual analog scale for pain severity measurement every 6 months until end of follow up.
- The treatment compliance will be assessed with the 8-item Morisky Medication Adherence Scale
- The patient’s health status will be evaluated at inclusion with the Onco-geriatric questionnaire G8, clinical score to predict the early death at 100 days, Lee score, ADL, IADL, HS, Charlson, MNA, percentage of weight loss, MMSE, GDSA, Balducci, walking speed and then at 2 and 6 months and progression with the Onco-geriatric questionnaire MMSE, ADL, IADL, walking speed, percentage of weight loss, HS.
研究者
Director of the Delegation for Clinical Research
Scientific
Centre Antoine Lacassagne