Clinical trial NCT05319314: GCC19CART for Patients With Metastatic Colorectal Cancer
Official title: A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of GCC19CART for Subjects With Relapsed or Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Colorectal Cancer
Keywords: relapsed metastatic colorectal cancer
refractory metastatic colorectal cancer
chimeric antigen receptors (CAR)
colorectal cancer
Lead sponsor: Innovative Cellular Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Study ICT-GCC19CART-US-001 (CARAPIA-1) is a Phase 1 study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of GCC19CART in subjects with relapsed or refractory metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* Adults \> 18 years old
* Clinical and histopathological diagnosis of metastatic colorectal cancer
* Guanylate Cyclase (GCC) positive disease as determined by immunohistochemistry (IHC). Positivity on staining of archival tumor tissue is adequate.
* Limited liver disease (less than 7 lesions with largest lesion less than 3 cm)
* No surgical options with curative intent.
* Received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in the advanced or metastatic setting, an anti-vascular endothelial growth factor (anti-VEGF) biological therapy if not contraindicated, and if RAS wild-type an anti-epidermal growth factor receptor (anti-EGFR) therapy in a manner consistent with National Comprehensive Cancer Network (NCCN) guidelines. Treatment must have been discontinued for disease progression or intolerance to therapy.
* Have at least one extracranial measurable target lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard.

Exclusion Criteria:

* Subjects with tumor lesion(s) in a location that may cause perforation of an organ or structure (such as the digestive track, urinary bladder, or blood vessel) with GCC19CART therapy.
* No active infectious diseases or comorbid conditions that would interfere with safety or data quality.
* Subjects with active infection requiring systemic therapy or causing fever (temperature \> 38.1˚C) or subjects with unexplained fever (temperature \> 38.1˚C) within 7 days prior to enrollment (leukapheresis) and reconfirmed prior to the day of investigational product administration.
* Pregnant or breast-feeding women

Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study
timeFrame: Infusion (Day 0) up to Day 28
measure: Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
timeFrame: Infusion (Day 0) up to Day 28
measure: Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
timeFrame: Infusion (Day 0) up to Day 28
Secondary outcomes:
measure: Best overall response as measured by overall response rate based on the tumor size per Response Evaluation Criteria in Solid Tumors RECIST Version 1.1
timeFrame: Infusion (Day 0) up to approximately 12 months or until disease progression/recurrence
measure: Duration of Response (DOR)
timeFrame: Infusion (Day 0) up to approximately 12 months
measure: Progression Free Survival (PFS)
timeFrame: Day 30 (date of leukapheresis) up to approximately 13 months or until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first.
measure: Overall Survival (OS)
timeFrame: Day 30 (date of leukapheresis) up to approximately 13 months or until death from any cause
measure: Copy number of Guanylate Cyclase C (GCC) by Quantitative Polymerase Chain Reaction (qPCR)
timeFrame: Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months)
measure: Copy number of each individual CD19 by Quantitative Polymerase Chain Reaction (qPCR)
timeFrame: Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months)
measure: Cytokine level in serum
timeFrame: Infusion (Day 0) up to 12 months post treatment
measure: AUC0 - Tmax: The area under curve (AUC) from time zero to Tmax in peripheral blood (days x copies/μg)
timeFrame: Infusion (Day 0) up to 12 months post treatment
measure: AUCTmax - 28d and/or AUCTmax - 84d: The area under curve (AUC) from time Tmax to day 28 and/or AUCTmax - 84d or other disease assessment days, in peripheral blood (days x copies/μg)
timeFrame: Infusion (Day 0) up to 12 months post treatment
measure: AUC0 - 28d and/or AUC0 - 84d: The area under curve (AUC) from time zero to day 28 and/or day 84 in peripheral blood (days x copies/μg)
timeFrame: Infusion (Day 0) up to 12 months post treatment
measure: Cmax: The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (copies/μg)
timeFrame: Infusion (Day 0) up to 12 months post treatment
measure: Tmax: The time to reach maximum(peak) in peripheral blood or other body fluid drug concentration after single dose administration (days)
timeFrame: Infusion (Day 0) up to 12 months post treatment
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
Study officials:
References: