A Phase IIR/III Trial of Standard of Care Therapy With or Without Stereotactic Body Radiotherapy (SBRT) and/or Surgical Ablation for Newly Oligometastatic Breast Cancer
概览
- 阶段
- 2 期
- 干预措施
- Standard of Care (SOC)
- 疾病 / 适应症
- Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8
- 发起方
- NRG Oncology
- 入组人数
- 129
- 试验地点
- 327
- 主要终点
- Progression-free Survival (Phase II)
- 状态
- 已完成
- 最后更新
- 8天前
概览
简要总结
This randomized phase II/III trial studies how well standard of care therapy with stereotactic radiosurgery and/or surgery works and compares it to standard of care therapy alone in treating patients with breast cancer that has spread to one or two locations in the body (limited metastatic) that are previously untreated. Standard of care therapy comprising chemotherapy, hormonal therapy, biological therapy, and others may help stop the spread of tumor cells. Radiation therapy and/or surgery is usually only given with standard of care therapy to relieve pain; however, in patients with limited metastatic breast cancer, stereotactic radiosurgery, also known as stereotactic body radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue and surgery may be able to effectively remove the metastatic tumor cells. It is not yet known whether standard of care therapy is more effective with stereotactic radiosurgery and/or surgery in treating limited metastatic breast cancer.
详细描述
PRIMARY OBJECTIVES: I. Phase II: To determine whether ablation \[through stereotactic body radiation therapy (SBRT) (stereotactic radiosurgery) and/or surgical resection of all known metastases\] in oligometastatic breast cancer patients provides a sufficient signal for improved progression-free survival (PFS) to warrant full accrual to the Phase III portion of the trial. II. Phase III: To determine whether ablation (through SBRT and/or surgical resection of all known metastases) in oligometastatic breast cancer patients significantly improves overall survival (OS). SECONDARY OBJECTIVES: I. To evaluate treated metastasis control according to tumor receptor status \[estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)\], use of chemotherapy, surgery versus (vs.) ablative therapy, and number of metastases. II. To evaluate whether the addition of ablative metastasis directed therapy significantly reduces the number of distant recurrences (new metastases) in patients who progress according to tumor receptor status (ER, PR, HER-2); use of chemotherapy, and number of metastases. III. To evaluate adverse events in patients who receive ablative metastasis-directed therapy to all known metastases in addition to standard medical therapy compared with those treated with standard medical therapy alone. EXPLORATORY OBJECTIVE: I. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout the radiation therapy processes, including imaging, simulation, target and critical structure definition, treatment planning, image guidance, and delivery. TRANSLATIONAL RESEARCH OBJECTIVES: I. To determine whether \< 5 circulating tumor cells (CTCs) (per 7.5 ml of blood) is an independent prognostic (outcome) marker for improved PFS and OS in oligometastatic breast cancer. II. To determine whether \< 5 CTCs (per 7.5 ml of blood) is an independent predictive (response to therapy) marker for improved PFS and OS in oligometastatic breast cancer. III. To determine whether eliminating CTCs (0/7.5 ml of blood in patients with at least 2 CTCs at registration) is both a prognostic and predictive marker for improved PFS and OS. IV. To evaluate the prognostic and predictive properties of CTC count as a continuous measure of PFS and OS. V. To store material for retrospective analysis of circulating tumor deoxyribonucleic acid (ctDNA). VI. To store material for retrospective analysis of circulating micro-ribonucleic acid (RNA).
研究者
入排标准
入选标准
- •A patient cannot be considered eligible for this study unless all of the following conditions are met.
- •Pathologically confirmed metastatic breast cancer
- •Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis;
- •Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
- •Number of allowable metastases:
- •=\< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:
- •Peripheral lung
- •Osseous (bone)
- •Central lung
- •Abdominal-pelvic metastases (lymph node/adrenal gland)
排除标准
- •Patients with any of the following conditions are NOT eligible for this study.
- •Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
- •Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; previous RT dose, date, fraction size, must be reported
- •Metastases with indistinct borders making targeting not feasible
- •Note: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician's judgment will be required
- •Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)
- •Metastases located within 3 cm of the previously irradiated structures:
- •Spinal cord previously irradiated to \> 40 Gy (delivered in =\< 3 Gy/fraction)
- •Brachial plexus previously irradiated to \> 50 Gy (delivered in =\< 3 Gy/fraction)
- •Small intestine, large intestine, or stomach previously irradiated to \> 45 Gy (delivered in =\< 3 Gy/fraction)
研究组 & 干预措施
Standard of Care (SOC)
Standard of care systemic therapy at the discretion of the treating physician.
Standard of Care + Ablation
Standard of care systemic therapy plus ablation of all metastases by stereotactic body radiotherapy or surgery at the discretion of the treating physician.
干预措施: Stereotactic Body Radiotherapy
Standard of Care + Ablation
Standard of care systemic therapy plus ablation of all metastases by stereotactic body radiotherapy or surgery at the discretion of the treating physician.
干预措施: Surgery
结局指标
主要结局
Progression-free Survival (Phase II)
时间窗: From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months, then every six months to five years, then annually. Maximum follow-up at time of analysis was 63 months.
Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Median PFS is provided.
Overall Survival (Phase III)
时间窗: From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months and then annually. Maximum follow-up at time of analysis was 63 months.
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored).
次要结局
- Percentage of Participants With New Metastases(From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.)
- Percentage of Participants With Treated Metastasis Progression on the SOC + Ablation Arm(From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months. Two-year rates are provide here.)
- Number of Patients by Highest Grade Adverse Event Reported(From randomization to last follow-up. Follow-up schedule: Arm 1: 3 mos. after randomization / Arm 2: weekly during SBRT and the last day of SBRT; both arms: then every 3 mos. to 24 mos., then annually. Maximum follow-up at time of analysis was 63 months.)
- Progression-free Survival in the Presence or Absence of Circulating Tumor Cells (CTCs)(From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.)