A Phase II Study of Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer
概览
- 阶段
- 2 期
- 干预措施
- Ribociclib
- 疾病 / 适应症
- Locoregional Recurrence
- 发起方
- Oana Danciu
- 入组人数
- 200
- 试验地点
- 38
- 主要终点
- Recurrence Free Survival (RFS)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This is an open label, multicenter, single arm phase II study to evaluate the efficacy and safety of ribociclib and ET in patients with locoregional recurrence of HR-positive, HER2-negative breast cancer.
详细描述
Collection of Correlative Samples at First Recurrence (Stage I consent) If feasible, optional correlative blood and fresh tissue will be collected during surgical excision of their 1st recurrence. Patients should then complete radiation therapy if that is indicated. Enrollment to the Treatment Phase will occur within 6 months of the last local treatment, surgery or radiation treatment, whichever occurred last. Study Treatment (Stage II/ main consent) Treatment includes: 1. Ribociclib: Oral ribociclib at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. 2. Physician's Choice Endocrine Therapy: ET consists of one of the following: * Intramuscular fulvestrant * Oral anastrozole * Oral letrozole * Oral exemestane * Concomitant use with tamoxifen is not allowed. Ribociclib administration is planned for 36 months and ET administration is planned for 60 months.
研究者
Oana Danciu
Sponsor Investigator
Hoosier Cancer Research Network
入排标准
入选标准
- •Eligibility Criteria to Collect Optional Correlative Blood and Tissue at Local Recurrence
- •Written informed consent (stage I) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Male or female age ≥ 18 years at the time of consent.
- •Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
- •Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
- •Patient has locoregional recurrence of breast cancer: locoregional recurrence is defined as invasive recurrence in the ipsilateral breast, axilla, regional nodes, or chest wall.
- •Inclusion Criteria for Treatment Phase:
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Written informed consent (stage II/ main consent) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific screening procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Male or female age ≥ 18 years at the time of consent. NOTE: Both pre- and post-menopausal women are eligible. Post-menopausal status is defined as:
排除标准
- •for Treatment Phase:
- •Subjects meeting any of the criteria below may not participate in the study:
- •Patient with a known hypersensitivity to any of the excipients of ribociclib.
- •Patient who has received prior CDK4/6 inhibitor for recurrent disease. Patients who received a CDK4/6 inhibitor in the adjuvant setting may participate if they have been off therapy for at least 1 year prior to diagnosis of recurrent disease.
- •Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
- •Pregnant or breastfeeding or planning to become pregnant during the trial (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- •Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
- •Patients with distant metastases of breast cancer beyond regional lymph nodes as defined by AJCC (8th edition).
- •Treatment with any investigational drug within 30 days prior to registration or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. Enrollment or planned enrollment in another study that does not involve an investigational drug will be allowed at the discretion of the treating investigator.
- •Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
研究组 & 干预措施
Investigational Group
The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.
干预措施: Ribociclib
Investigational Group
The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.
干预措施: Fulvestrant
Investigational Group
The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.
干预措施: Anastrozole
Investigational Group
The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.
干预措施: Letrozole
Investigational Group
The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.
干预措施: Exemestane
结局指标
主要结局
Recurrence Free Survival (RFS)
时间窗: 3 years
Estimate subsequent recurrence-free survival (RFS) at 3 years for ribociclib when administered with ET (AIs or fulvestrant). RFS is defined as interval from registration until invasive or DCIS recurrence in the ipsilateral breast or locoregionally, invasive recurrence at a distant site, or death from breast cancer or any other cause, whichever occurs first. The censoring time is the completion of study at 6 years (3 years of patient accrual and 3 years of follow up time). The RFS at 3 years will be also treated as the primary endpoint in the power and sample size calculation.
次要结局
- Distant Metastasis-Free Survival(3 years)
- Overall Survival (OS)(3 years)
- Assess adverse events(3 months)