MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

Phase 1TerminatedNCT02391038

Millennium Pharmaceuticals, Inc.12 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Interventions

MLN0264DRUG

MLN0264 IV.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

Locations (4)

Unnamed facility

Kashiwa-shi, Chiba, Japan

Unnamed facility

Minatoku, Tokyo-To, Japan

Unnamed facility

Seoul, Gyeonggi-do, South Korea

Unnamed facility

Taipei, Taipei, Taiwan

Outcomes

Primary Outcomes

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

Time frame: 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)

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

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

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.

Time frame: Phase 1: Up to Cycle 1 (3 weeks)

Phase 1- Number of Participants With Markedly Abnormal Laboratory Values

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.

Time frame: 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

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 \[bpm\]).

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

Phase 1- Recommended Phase 2 Dose (RP2D)

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.

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

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