A Phase II Clinical Trial of Neoadjuvant Zanidatamab for HER2+ Localized Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Rate of Complete and Major Pathologic Regression (Cohort 1)
研究概览
简要总结
This phase II trial studies how well giving zanidatamab before surgery (neoadjuvant) works in treating patients with colon and rectal cancer that is human epidermal growth factor receptor 2 positive (HER2+ve) who are planned for curative intent treatment. Zanidatamab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens).
详细描述
PRIMARY OBJECTIVE:
I. To determine the activity of neoadjuvant zanidatamab in HER2+ve (RAS wild type [RAS WT]) locally advanced colorectal cancer.
SECONDARY OBJECTIVES:
I. To determine the efficacy of neoadjuvant zanidatamab in HER2+ve (RAS WT) locally advanced colorectal cancer.
II. To determine the feasibility and safety of neoadjuvant zanidatamab in human epidermal growth factor receptor 2 positive (HER2+) locally advanced colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 or cytologically confirmed colon and/or rectal cancer planned for curative intent treatment at gastrointestinal clinics of Emory University's Winship Cancer Institute and collaborating centers
- •Tumors must be HER2+ve (human epidermal growth factor receptor 2 [HER2] overexpression 3+ immunohistochemistry [IHC] or 2+ by IHC and positive fluorescence in situ hybridization [FISH] or HER2 amplification by next generation sequencing)
- •Tumors must have RAS wildtype genotype
- •Radiologically measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)
- •Platelet count > 100,000 cells/ ul (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Hemoglobin > 9g/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Absolute neutrophil count > 1000 cells/dl (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Alanine aminotransferase (ALT) ≤ 3 × ULN (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Total bilirubin ≤ 1.5 × ULN, or ≤ 3 × ULN for participants with Gilbert's disease (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Glomerular filtration rate (GFR) > 60ml/min (based on creatine, and Cystatin C estimation where applicable) (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Adequate cardiac function with left ventricular ejection fraction of at least 50% (within 28 days of cycle 1 day 1, at the discretion of the investigator)
- •Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
- •FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- •Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. This includes willingness to undergo mandatory blood sample draws for evaluation of correlatives
- •Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
排除标准
- •Participants with stage IV colon and rectal cancer even if curative intent resection is planned
- •HER2 expression that does not meet documented inclusion criteria
- •RAS mutation
- •MSI-H or mismatch repair deficient rectal cancer
- •Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). Participants with known myocardial infarction or unstable angina within 6 months prior to expected date of cycle 1 day 1 (C1D1) are also excluded. Previous anticancer therapy-related CHF must have been ≤ grade 1 at the time of occurrence and must have completely resolved
- •Participants receiving any other investigational agents or an investigational device within 28 days of administering the first dose of study drug
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study
- •Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
研究组 & 干预措施
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Zanidatamab (Biological)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Resection (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Patient Observation (Other)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Zanidatamab (Biological)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Echocardiography Test (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Multigated Acquisition Scan (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Endoscopic Procedure (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Computed Tomography (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Biospecimen Collection (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Biopsy Procedure (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Digital Rectal Examination (Procedure)
Cohort 1 (zanidatamab, surgical resection)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection on study followed by adjuvant chemotherapy as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT or MRI, and blood sample collection throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Electronic Health Record Review (Other)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Resection (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Patient Observation (Other)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Echocardiography Test (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Multigated Acquisition Scan (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Endoscopic Procedure (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Computed Tomography (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Biospecimen Collection (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Biopsy Procedure (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Digital Rectal Examination (Procedure)
Cohort 2 (zanidatamab)
Patients receive zanidatamab IV over 90-150 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients then optionally undergo surgical resection or observation as per standard of care. Additionally, patients undergo echocardiography or MUGA scan, sigmoidscopy, CT, MRI, blood sample collection, and digital rectal exam throughout the study. Patients also undergo archival tissue sample collection or biopsy during screening.
干预措施: Electronic Health Record Review (Other)
结局指标
主要结局
Rate of Complete and Major Pathologic Regression (Cohort 1)
时间窗: At time of surgical resection
For colon cancer, will evaluate the rate of complete and major pathologic regression in the surgical specimen based on the modified Dworak grading system. Will be reported as a proportion, and 95% exact binomial confidence interval. Will be estimated using the Clopper-Pearson method.
Radiologic Response (Cohort 2)
时间窗: At 6 and 12 weeks
Assessment will be by computed tomography chest, abdomen and magnetic resonance imaging of the rectum. Radiologic tumor response will be based on Response Evaluation Criteria in Solid Tumors 1.1. Will be reported as a proportion, and 95% exact binomial confidence interval. Will be estimated using the Clopper-Pearson method.
Tumor Regression Grades (Cohort 2)
时间窗: At time of surgical resection
Will be assessed in those who undergo surgical resection.
次要结局
- Rate of Circulating Tumor Deoxyribonucleic Acid Clearance(Before cycle 1 day 1 of treatment and preoperatively for colon cancer patients or at 6 and 12 weeks for rectal cancer patients)
- Rate of Tumor Recurrence(At 2 years)
- Rate of Perioperative Complications (Feasibility)(Up to 3 years)
- Recurrence Free Survival(At 2 years)
- Incidence of Adverse Events(Up to 30 days post-discontinuation)
- Proportion of Subjects who Complete Four Treatment Cycles (Feasibility)(Up to 3 years)
- Adverse Even Profile (Feasibility)(Up to 3 years)
研究者
Olumide Gbolahan
Principal Investigator
Emory University