Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Interventions
investigational material(s)
Generic name etc : MLN0264
INN of investigational material :
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material
Sponsors
TAKEDA PHARMACEUTICAL COMPANY LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Has Diagnosis of GI carcinoma with IHC evidence of expression of GCC protein (Hscore 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 least4 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 RECIST version 1.1 guidelines - Has Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to enrolment) - 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 NCI CTCAE version 4.03
Exclusion criteria
Exclusion criteria: - Has resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by NCI CTCAE version 4.03 - Has Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent - Female patients 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 ECG abnormalities considered by the investigator to be clinically -significant, or repeated baseline prolongation of the rate-corrected QT interval (millisec) of electrocardiograph the (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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events, DLTs, Markedly Abnormal Laboratory Values in Phase 1, Vital Sign in Phase 1, Recommended Dose for Use in Study Phase II, Pharmacokinetics of MLN0264, Serum concentrations of Total Antibody and monoethyl auristatin E, Overall response rate of Asian patients with recurrent or metastatic GCC-positive adenocarcinoma of the stomach or gastroesophageal junction treated with MLN0264 Up to Month 46 in all | — |
Secondary
| Measure | Time frame |
|---|---|
| Presence of Antitherapeutic Antibodies (ATA) in the Serum, Disease response based on the investigator's assessment, Adverse Events in Phase 2, Clinically Significant Laboratory Values in Phase 2, Vital Sign in Phase 2, Participant Progression-Free Survival (PFS) in Phase 2, Duration of Response (DOR) in Phase 2, Disease Control Rate (DCR) in Phase 2, Participant Overall Survival (OS) in Phase 2, Pharmacokinetics of MLN0264 (Phase 2), Tumor Size, Assessment of Participant GCC H-score Up to Month 37 in all | — |
Outcome results
None listed