Metastatic Colorectal Cancer
Conditions
Brief summary
A Phase 1b Dose Escalation Study of the Safety and Pharmacodynamics of Brontictuzumab in Combination with Chemotherapy for Subjects with Previously Treated Metastatic Colorectal Cancer.
Detailed description
This is a phase 1b dose escalation study of the safety and pharmacodynamics of brontictuzumab in combination with chemotherapy for subjects with previously treated metastatic colorectal cancer. This study consists of a screening period, a treatment period and a post-treatment follow up period in which patients will be followed for survival for up to 24 months. Patients will be enrolled in two stages: a dose-escalation stage and an expansion phase. Approximately 34 patients will be enrolled in this study at approximately 5 study centers in the United States.
Interventions
DRUGbrontictuzumab
starting dose of 1.5mg/kg administered intravenously (IV)
DRUGtrifluridine/tipiracil
Sponsors
OncoMed Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if KRAS wild-type, an anti-EGFR therapy * ECOG performance status 0 or 1
Exclusion criteria
* Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors * Subjects with known active HIV infection. Subjects with HIV that are under a stable anti-retroviral regimen and have no evidence of immune deficiency (normal CD4 counts), undetectable viral load, and no HIV-related infections are eligible * Subjects with uncontrolled diarrhea \<30 days prior to first administration of study drug * Subjects with any history of or current clinically significant gastrointestinal disease including, but not limited to: * Inflammatory bowel disease (including ulcerative colitis and Crohn's disease) * Active peptic ulcer disease * Known intraluminal metastatic lesion(s) with risk of bleeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with adverse events | up to approximately 2 years |
| Percentage of patients with dose limiting toxicities | 28 days |
| Percentage of patients with anti-brontictuzumab antibodies | up to approximately 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | approximately 2 years |
| Changes in number of circulating tumor cells | approximately 2 years |
| Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | approximately 2 years |
| Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 | approximately 2 years |
Countries
United States
Outcome results
None listed