Clinical trial NCT03031691: A Study of Brontictuzumab With Chemotherapy for Subjects With Previously Treated Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Mereo BioPharma
Sponsor class: INDUSTRY
First posted: 2017-01-25
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients with adverse events
timeFrame: up to approximately 2 years
measure: Percentage of patients with dose limiting toxicities
timeFrame: 28 days
measure: Percentage of patients with anti-brontictuzumab antibodies
timeFrame: up to approximately 2 years
Secondary outcomes:
measure: Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: approximately 2 years
measure: Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1
timeFrame: approximately 2 years
measure: Changes in number of circulating tumor cells
timeFrame: approximately 2 years
measure: Overall survival
timeFrame: approximately 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver
state: Colorado
city: Miami
country: United States
facility: Miami
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Charleston
country: United States
facility: Charleston
state: South Carolina
city: Nashville
country: United States
facility: Nashville
state: Tennessee
Study officials:
References: