An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 672
- 主要终点
- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)
研究概览
简要总结
This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also determine what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).
Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:
- mFOLFOX6 alone,
- mFOLFOX6 with bevacizumab, or
- mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
- •Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
- •If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
- •HER2+ disease as determined by a tissue based assay performed at a central laboratory.
- •Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
- •Radiographically measurable disease per RECIST v1.1 with:
- •At least one site of disease that is measurable and that has not been previously irradiated, or
- •If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:
- •No evidence of brain metastases
- •Previously treated brain metastases which are asymptomatic
排除标准
- •Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
- •Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
- •Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
- •Previous treatment with anti-HER2 therapy
- •Ongoing Grade 3 or higher neuropathy
- •Active or untreated gastrointestinal (GI) perforation at the time of screening.
研究组 & 干预措施
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: tucatinib (Drug)
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: leucovorin (Drug)
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: levoleucovorin (Drug)
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: trastuzumab (Drug)
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: oxaliplatin (Drug)
Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
干预措施: fluorouracil (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: levoleucovorin (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: cetuximab (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: bevacizumab (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: oxaliplatin (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: fluorouracil (Drug)
Standard of Care Arm
Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
干预措施: leucovorin (Drug)
结局指标
主要结局
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 3 years
The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause
次要结局
- Duration of response (DOR) per RECIST v1.1 by BICR(Up to approximately 3 years)
- DOR per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- Time to second progression or death (PFS2)(Up to approximately 3 years)
- Incidence of adverse events (AEs)(Through 30 days after the last study treatment; approximately 1 year)
- Trough concentration (Ctrough)(Approximately 4 months)
- Overall survival (OS)(Up to approximately 6 years)
- Confirmed objective response rate (cORR) per RECIST v1.1 by BICR(Up to approximately 3 years)
- PFS per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- cORR per RECIST v1.1 by investigator assessment(Up to approximately 3 years)
- Incidence of dose alterations(Through 30 days after the last study treatment; approximately 1 year)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score(Through 30-37 days after the last study treatment; approximately 1 year)
- Time to meaningful change in EORTC QLQ30 score(Through 30-37 days after the last study treatment; approximately 1 year)