CARAPIA-1: GCC19CART for Patients With Metastatic Colorectal Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GCC19CART Single infusion of GCC19CART at the dose assigned to an individual subject. All subjects will receive the same investigational therapy with the dose administered dependent upon the dose level they are assigned to in a sequential manner. Two dose level escalations are planned with one dose de-escalation listed if needed. |
Drug: GCC19CART
Single infusion of Chimeric Antigen Receptor (CAR) transduced autologous T cells administered intravenously (i.v.)
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study [Infusion (Day 0) up to Day 28]
- Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study [Infusion (Day 0) up to Day 28]
- Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study [Infusion (Day 0) up to Day 28]
Secondary Outcome Measures
- 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 [Infusion (Day 0) up to approximately 12 months or until disease progression/recurrence]
- Duration of Response (DOR) [Infusion (Day 0) up to approximately 12 months]
The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
- Progression Free Survival (PFS) [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.]
Progression free survival (PFS) time which is defined as time from date of leukapheresis until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first.
- Overall Survival (OS) [Day 30 (date of leukapheresis) up to approximately 13 months or until death from any cause]
Overall survival (OS) is defined as the time from the date of leukapheresis until death from any cause.
- Copy number of Guanylate Cyclase C (GCC) by Quantitative Polymerase Chain Reaction (qPCR) [Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months)]
- Copy number of each individual CD19 by Quantitative Polymerase Chain Reaction (qPCR) [Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months)]
- Cytokine level in serum [Infusion (Day 0) up to 12 months post treatment]
- AUC0 - Tmax: The area under curve (AUC) from time zero to Tmax in peripheral blood (days x copies/μg) [Infusion (Day 0) up to 12 months post treatment]
- 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) [Infusion (Day 0) up to 12 months post treatment]
- 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) [Infusion (Day 0) up to 12 months post treatment]
- Cmax: The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (copies/μg) [Infusion (Day 0) up to 12 months post treatment]
- Tmax: The time to reach maximum(peak) in peripheral blood or other body fluid drug concentration after single dose administration (days) [Infusion (Day 0) up to 12 months post treatment]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults > 18 years old
-
Clinical and histopathological diagnosis of metastatic colorectal cancer Guanylate Cyclase (GCC) positive metastatic disease as determined by immunohistochemistry (IHC) from a new biopsy of a proposed target lesion.
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Limited liver disease (less than 5 lesions with largest lesion less than 3 cm)
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No surgical options with curative intent.
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Received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in the metastatic setting (or palliative therapy within 12 months of adjuvant therapy), 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.
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Have at least two extracranial measurable target lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard.
Exclusion Criteria:
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Subjects with unresectable or metastatic microsatellite instability-high or mismatch repair deficient tumors.
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No active infectious diseases or comorbid conditions that would interfere with safety or data quality.
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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 the day of investigational product administration.
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Pregnant or breast-feeding women
Other protocol defined Inclusion/Exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco Medical Center | San Francisco | California | United States | 94143 |
| 2 | University of Colorado Hospital - Anschutz Cancer Pavilion | Aurora | Colorado | United States | 80045 |
| 3 | University of Florida | Gainesville | Florida | United States | 32610 |
| 4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215-5418 |
| 5 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
| 6 | Baylor Scott & White Research Institute | Dallas | Texas | United States | 75204 |
Sponsors and Collaborators
- Innovative Cellular Therapeutics Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ICT-GCC19CART-US-001