A Single-arm Phase II Study of Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma Who Failed a Platinum-based Chemotherapy

National Taiwan University Hospital1 site in 1 country24 target enrollmentJune 23, 2021

ConditionsEsophageal Cancer Metastatic Cancer Squamous Cell Carcinoma

InterventionsCabozantinib 40 MG Atezolizumab Injection

Overview

Phase: Phase 2
Intervention: Cabozantinib 40 MG
Conditions: Esophageal Cancer
Sponsor: National Taiwan University Hospital
Enrollment: 24
Locations: 1
Primary Endpoint: Overall response rate (ORR)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

To demonstrate that combination of cabozantinib and atezolizumab is safe and efficacious in patients with recurrent/metastatic esophageal squamous cell carcinoma.

Detailed Description

Patients with histologically proven squamous cell carcinoma of esophagus and had progression from first-line platinum-based chemotherapy for recurrent or metastatic ESCC, or progression within 6 months after neoadjuvant, definitive, or adjuvant chemo(radio) -therapy for loco-regional ESCC would be eligible for this trial. Eligible patients will receive daily 40mg cabozantinib plus i.v. atezolizumab 1200mg Q3W for treatment response evaluation. Primary endpoint is the objective response rate, and secondary endpoints include progression-free survival, overall survival, and safety profiles.

Registry

clinicaltrials.gov

Start Date

June 23, 2021

End Date

December 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Taiwan University Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•1.Histologically proven squamous cell carcinoma of esophagus.
•2.Progression from first-line platinum-based chemotherapy for recurrent or metastatic ESCC, or progression within 6 months after neoadjuvant, definitive, or adjuvant chemo(radio) -therapy for loco-regional ESCC.
•3.Measurable disease per RECIST 1.1
•4.Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy as determined by the Investigator.
•5.Age twenty years or older
•6.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•7.The subject is receiving antiviral therapy per local standard of care if the subject has active HBV infection (defined by HBsAg positive); the subject must have HBV DNA \< 500 IU/mL.Patients with HBV infection are required to continue antiviral therapy throughout the Treatment Period, and till at least 3 months after discontinuing Trial treatment.
•8.Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days prior to treatment:
•Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support within 2 weeks before screening laboratory sample collection.
•White blood cell (WBC) count ≥ 2500/µL.

Exclusion Criteria

•1.Previously treated with PD-1/PD-L1 blockade or any type of small molecule kinase inhibitor (including investigational kinase inhibitor)
•2.Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
•3.Prior radiotherapy regimen exceeding 70 Gy for a single site, including ESCC or other metastatic sites:
•For radiotherapy to treat ESCC:
•If the radiation is combined with chemotherapy, a minimum of 4 months must elapse between the end of radiotherapy and registration. If the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration.
•For radiotherapy to treat metastatic site:
•A minimum of 3 weeks must elapse between prior radiation and registration.
•All treatment areas should be fully healed with no sequelae from RT that would predispose to fistula formation. Unhealed or with sequelae from RT that would predispose to fistula formation.
•4.Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
•5.Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel), except for the following allowed anticoagulants:

Arms & Interventions

cabozantinib plus atezolizumab

cabozantinib 40mg PO QD atezolizumab 1200mg IVD 30-60mins Q3W

Intervention: Cabozantinib 40 MG

cabozantinib plus atezolizumab

cabozantinib 40mg PO QD atezolizumab 1200mg IVD 30-60mins Q3W

Intervention: Atezolizumab Injection

Outcomes

Primary Outcomes

Overall response rate (ORR)

Time Frame: at least 3 weeks after the first treatment

Overall response rate (ORR) is the proportion of patients whose tumor is significantly reduced.

Secondary Outcomes

Progression-free survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
Overall survival(From date of randomization until the date of death from any cause, assessed up to 60 months)
Safety (treatment-related adverse effects)(From the first treatment to 30 days after the end of study.)