A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 53
- 主要终点
- Part 1: Number of Participants With Dose-limiting Toxicities
研究概览
简要总结
This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.
详细描述
This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.
The objective for Part 1 is to identify a tolerable dose of conatumumab in combination with panitumumab based on the incidence of dose-limiting toxicities in patients with Metastatic Colorectal Cancer.
The objective for Part 2 is to evaluate the objective response rate stratified by Kirsten Rat Sarcoma Virus Oncogene (KRAS) status (wild-type versus mutant) in patients with Metastatic Colorectal Cancer treated with the combination of panitumumab and conatumumab (tolerable dose identified in part 1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 metastatic adenocarcinoma of the colon or rectum
- •Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.
- •At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory
- •Man or woman ≥ 18 years of age at the time of enrollment
- •Hematologic function within the following limits:
- •Absolute neutrophil count (ANC) > 1.0 x 10^9 cells/L
- •Platelets ≥ 100 x 10^9/L
- •Renal function within the following limits:
- •Creatinine < 2.0 mg/dL
- •Hepatic function within the following limits:
- •Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
- •Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
- •Bilirubin ≤ 2 x ULN
- •Metabolic function within the following limits:
- •Amylase ≤ 2 x ULN
- •Lipase ≤ 2 x ULN
- •Magnesium ≥ lower limit of normal
- •Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)
- •Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer
- •Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent
排除标准
- •History of other primary cancer, unless:
- •Curatively resected non-melanomatous skin cancer
- •Curatively treated cervical carcinoma in situ
- •Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment
- •Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment
- •Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment
- •Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment
- •Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment
- •Any investigational agent or therapy ≤ 30 days before enrollment
- •Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655
- •History of or known presence of central nervous system (CNS) metastases
- •History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment
- •Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events [CTCAE] grade 2 [CTCAE version 3.0])
- •Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
- •Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)
- •Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results
- •Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities.
- •Other investigational procedures are excluded
- •Patient is currently pregnant or breast feeding
- •Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.
- •Previously enrolled into this study
- •Patient unwilling or unable to comply with study requirements
研究组 & 干预措施
Panitumumab plus conatumumab
Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
干预措施: Panitumumab (Drug)
Panitumumab plus conatumumab
Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
干预措施: Conatumumab (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose-limiting Toxicities
时间窗: 4 weeks
A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.
Number of Participants With an Objective Response
时间窗: Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.
次要结局
- Progression-free Survival(Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).)
- Number of Participants With Disease Control(Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).)
- Duation of Response(Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).)
- Number of Participants With Anti-therapeutic Antibodies(Antibody samples were collected at weeks 1, 7, and 23 and every 6 months thereafter during treatment, and at the safety follow-up and follow-up visits. The mean follow-up time was 35.7 weeks.)
- Overall Survival(Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).)
- Time to Response(Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).)
- Number of Participants With Adverse Events (AEs)(From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.)
- Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher(From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.)