A Phase 2, Multicenter, Two Tier Study of IMC-A12 in Combination With Depot Octreotide in Patients With Metastatic, Well or Moderately Differentiated Carcinoid or Islet Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months
研究概览
简要总结
Determine the 6-month progression free survival (PFS) rate associated with cixutumumab in combination with depot octreotide acetate (octreotide) in participants with metastatic neuroendocrine tumors.
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
- •The participant has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors
- •The participant has metastatic disease at the time of study entry
- •The participant must have a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, measurable by elevated tumor markers (eg, 24-hour urine 5-HIAA, chromogranin A, adrenocorticotropin hormone (ACTH), gastrin, or other tumor specific biochemical markers), or both
- •The participant is age ≥ 18 years
- •The participant's tumor has Ki-67 expression ≤ 20%
- •The participant is receiving depot octreotide therapy at the time of enrolling into the study
- •The participant has received 0 - 2 systemic anticancer regimens in addition to depot octreotide, which may have included chemotherapy, interferon, antiangiogenic therapy, other targeted treatments, or a combination of such treatments
- •The participant is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy
- •The participant has experienced radiographic, biochemical, and/or scintigraphic disease progression while on a regimen that includes octreotide
- •The participant has completed prior chemotherapy and/or radiotherapy with curative intent at least 3 weeks prior to the administration of the first dose of study therapy. Participants that have received palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible
- •The participant has a life expectancy of > 3 months
- •The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
- •The participant has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/microliters (μL), hemoglobin ≥ 9 gram/deciliter (g/dL), and platelet count ≥100,000/μL
- •The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
- •The participant either has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the ULN, or is on a stable dose of anticoagulant
- •The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliter/minute (mL/min) for participants with creatinine levels above the ULN
- •The participant has fasting serum glucose < 160 milligram/deciliter (mg/dL) and hemoglobin A1c (HgbA1c)≤
- •If baseline nonfasting glucose is < 160 mg/dL, fasting glucose measurement is not required
- •Because the teratogenicity of cixutumumab is not known, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- •The participant has the ability to understand and the willingness to sign a written informed consent document
排除标准
- •The participant has uncontrolled brain or leptomeningeal metastases
- •The participant has not recovered to Grade ≤ 1 from adverse events due to agents administered more than 4 weeks prior to study entry (except for alopecia)
- •The participant is receiving any other investigational agent(s)
- •The participant has received therapeutic radiolabeled somatostatin analogues
- •The participant has received more than 2 prior regimens of systemic therapy in the metastatic setting
- •The participant has a history of treatment with other agents targeting the IGF receptor
- •The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of cixutumumab or to octreotide
- •The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their fasting glucose < 160 mg/dL or below the ULN and that they are on a stable dietary or therapeutic regimen for this condition
- •The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •The participant is pregnant or lactating
- •The participant is known to be positive for infection with the human immunodeficiency virus
- •The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected or treated with no known active disease present and no treatment administered for the last 3 years
研究组 & 干预措施
Carcinoid tumor
Participants with carcinoid tumor will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
干预措施: Cixutumumab (Biological)
Carcinoid tumor
Participants with carcinoid tumor will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
干预措施: depot octreotide (Drug)
Islet cell carcinoma
Participants with islet cell carcinoma will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
干预措施: Cixutumumab (Biological)
Islet cell carcinoma
Participants with islet cell carcinoma will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
干预措施: depot octreotide (Drug)
结局指标
主要结局
Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months
时间窗: From Start of Study Treatment to Progressive Disease or Death Due to Any Cause (Up to 6 Months)
Percentage of participants who are alive and progression-free at 6 month from start of the study treatment over all participants. PFS is defined as the time from the start of study treatment until the date of objectively determined progressive disease (PD) or death due to any cause. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS was estimated by the binomial distribution and Kaplan-Meier method.
次要结局
- Percentage of Participants Who Achieve Modified Objective Response Rate (ORR) of Complete Response (CR), Partial Response (PR) and Minor Response (MR) Modified Objective Response Rate (mORR)(From Start of Treatment Baseline to Disease Progression (Up to 18 Months))
- Percentage of Participants With a Biochemical Response Rate(From Start of Treatment Up to 18 Months)
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)(18 months)
- Pharmacokinetics (PK): Maximum Concentration (Cmax) Cycle 1(Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion)
- PK: Half-life (t 1/2) Cycle 1(Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion)
- PK: Area Under Concentration (AUCinf) Cycle 1(Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion)
- PK: Clearance (CL) Cycle 1(Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion)
- PK: Volume at Steady State (Vss) Cycle 1(Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion)
- Serum Anti-Cixutumumab Antibody Assessment(18 months)
- Pharmacodynamics Markers; Concentration of Insulin-like Growth Factor I, II (IGF-I, IGF-II), IGF Body Fat (IGFBF)-1 and IGFBF-2(18 months)