A Phase 1/2 Trial of MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC)

Millennium Pharmaceuticals, Inc.0 个研究点目标入组 12 人开始时间: 2014年12月最近更新: 2017年3月29日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Millennium Pharmaceuticals, Inc.
入组人数: 12
主要终点: Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the effects of MLN0264 in previously treated Asian participants with Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC).

详细描述

The drug being tested in this study is called MLN0264. This drug is being evaluated to check the effects on previously treated Asian individuals with Advanced GI Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2). The study will enroll approximately 95 participants.

In Phase 1, approximately 14 Asian participants with GI malignancies will be enrolled in 3 planned dose cohorts according to the traditional 3 + 3 dose escalation scheme. The starting dose will be 1.2 mg/kg of MLN0264 administered IV on Day 1 of 3-week cycles for up to 1 year or until disease progression or unacceptable toxicity occurs. Dose escalation will take place until Phase 2 recommended dose is determined.

In Phase 2, eligible Asian participants with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction will be enrolled. Participants must have failed at least 2 lines of prior anticancer therapy for advanced or metastatic disease. Disease recurrence within 6 months of the last dose of post-surgical adjuvant chemotherapy counts as 1 line of prior anticancer therapy for advanced disease.

This multi-center trial will be conducted in Japan, Korea and Taiwan. The overall time to participate in this study is up to 3 years.

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

•Has Diagnosis of GI carcinoma with Immunohistochemistry/ Immunohistochemical (IHC) evidence of expression of GCC protein (H-score of 10 or greater), for which standard treatment is no longer effective or does not offer curative or life-prolonging potential.
•Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment (except for Avastin [bevacizumab] for which at least 8 weeks from its last administration should elapse prior to enrollment).
•Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the stomach or gastroesophageal junction with IHC evidence of expression of GCC indicated by an H-score of 10 or greater.
•Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment.
•Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
•Has Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to enrollment).
•Females must be 1-year postmenopausal, or even if surgically sterile, agree to use other acceptable forms of birth control.
•Has adequate organ and hematological function.
•Has resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

排除标准

•Has Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent.
•Female participants who are in the lactation period, even if they discontinue breastfeeding, or have a positive pregnancy test during the Screening period.
•Has uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months prior to enrollment.
•Has treatment with any medication that has a clinically relevant potential risk of prolonging the QT interval or inducing Torsades de Pointes that cannot be discontinued or switched to a different medication prior to starting study drug.
•Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically -significant, or repeated baseline prolongation of the rate-corrected QT interval millisecond (msec) of electrocardiograph (QTc).
•Ongoing or clinically significant active infection.
•Has signs of peripheral neuropathy.
•Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment.
•Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug.
•Has any preexisting medical condition of sufficient severity to prevent full compliance with the study.
•Has past or concurrent history of neoplasm other than GI carcinoma (phase 1) or gastric adenocarcinoma (phase 2), except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri.
•Known diagnosis of human immunodeficiency virus (HIV) infection.
•Has asymptomatic brain metastases.
•Has an alcohol or substance abuse disorder.
•Has positive test for hepatitis B surface antigen.
•History of hypersensitivity to any ingredient of MLN0264.

研究组 & 干预措施

MLN0264

Experimental

Phase 1: MLN0264 1.2 milligram per kilogram (mg/kg) starting dose, Intravenous (IV), on Day 1 of 3 week cycles, for up to 1 year or until disease progression or unacceptable toxicity. Dosage of MLN0264 will be increased to 1.5 mg/kg then 1.8 mg/kg using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 Dose (RP2D).

Phase 2: MLN0264, IV, on Day 1 of 3 week cycles, for up to 1 year or until disease progression or unacceptable toxicity. Dosage for this phase will be determined from results of Phase 1 MTD/RP2D.

干预措施: MLN0264 (Drug)

结局指标

主要结局

Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

时间窗: Phase 1: Up to Cycle 1 (3 weeks)

Toxicity evaluated as per NationalCancerInstituteCommonTerminologyCriteria for AEs (NCI CTCAE),version 4.03.DLT=any event related to MLN0264:Grade 4 neutropenia(absolute neutrophil count\[ANC\]less than\[\<\]500 cells/millimeter\[mm\]\^3); \>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle greater than (\>)2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

Phase 1- Number of Participants With Markedly Abnormal Laboratory Values

时间窗: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation.

Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)

时间窗: Phase 1: Baseline through 30 days after the last dose of study drug (approximately up to 35 weeks)

Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE)

时间窗: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs

时间窗: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]).

Phase 1- Recommended Phase 2 Dose (RP2D)

时间窗: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

RP2D is maximum tolerated dose(MTD) in study Phase1.MTD was highest dose of MLN0264 given at which \<=1 of 6 participants experienced DLTduring Cycle1 of Phase1.DLT=any event related to MLN0264:Grade 4 neutropenia ANC less than\<500 cells mm\^3;\>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle\>2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264

时间窗: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264