A Phase II Clinical Trial of Bevacizumab Plus eRlotinIb in patientS With Advanced Cancer Having Genetic Alterations in Krebs Cycle (BRISK, KCSG AL22-16)

Asan Medical Center10 sites in 1 country32 target enrollmentJanuary 2, 2023

ConditionsSolid Tumors Advanced Solid Tumors Metastatic Cancer

Interventionsbevacizumab erlotinib

Drugsbevacizumab erlotinib

Overview

Phase: Phase 2
Intervention: bevacizumab
Conditions: Solid Tumors
Sponsor: Asan Medical Center
Enrollment: 32
Locations: 10
Primary Endpoint: Objective response rate
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A national, prospective, multi-center, open-label, single arm phase II trial investigating the efficacy and safety of bevacizumab plus erlotinib in patients with advanced cancers which harbors genomic alterations in Krebs cycle

Detailed Description

The BRISK study will recruit patients with locally advanced or metastatic solid tumor harboring the genomic alterations in Krebs cycle (e.g. fumarate hydratase, isocitrate dehydrogenase, succinate dehydrogenase) who had disease progression on standard systemic treatment and/or has no standard treatment option, and investigate the efficacy and safety of bevacizumab plus erlotinib.

Registry

clinicaltrials.gov

Start Date

January 2, 2023

End Date

January 31, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Asan Medical Center

Responsible Party

Principal Investigator

Inkeun Park

Clinical Associate Professor

Asan Medical Center

Eligibility Criteria

Inclusion Criteria

•Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the KOSMOS-II master trial
•Age 19 or more
•Histologically confirmed solid cancer
•Genetic alteration in genes related to Krebs cycle (fumarate hydratase, succinate dehydrogenase, isocitrate dehydrogenase, or maleate dehydrogenase 2). Only pathogenic and likely pathogenic variant in either germline or somatic gene will be permitted.
•Patients with locally advanced, recurrent, or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent
•Disease progressed during or after standard treatment with no further treatment option, no standard treatment, patient's refusal to receive standard treatment, or unfit for standard treatment. If standard treatment contains bevacizumab and/or erlotinib, patient can be included according to treating physician's discretion
•Measurable disease according to RECIST v1.1 criteria
•ECOG performance status 0 or 2
•Adequate bone marrow, hepatic, and renal function Hematology
•Neutrophil \>= 1,500/mm3

Exclusion Criteria

•Previous treatment with combination of vascular endothelial growth factor inhibitors and epithelial growth factor receptor inhibitors. Previous exposure to only VEGF inhibitor or EGFR inhibitor, or sequential exposure to both agents can be included at the treating physician's discretion
•Previous radiotherapy to the only measurable lesion: but previous radiotherapy will be permitted unless the lesion is the only measurable lesion
•Uncontrolled CNS metastasis (brain and/or leptomeningeal metastasis) that requires anti-edema drugs such as steroid for symptoms or symptom management. Primary CNS malignancy such as glioblastoma can be included by treating physician's discretion.
•Have clinically problematic cardiovascular diseases, such as unstable angina, congestive heart failure, advanced arrhythmia requiring treatment with medication, or a history of myocardial infarction within 12 months prior to enrollment. Inclusion is allowed if patient has no evidence of active disease for at least 6 months prior to enrollment.
•Inadequately controlled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 100 mmHg on anti-hypertensive medications).
•History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to screening
•History of bleeding diathesis or coagulopathy
•Urine dipstick proteinuria≥2+ or urine protein/creatinine ratio \>1.
•If patients are discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of proteinuria in 24 hours.
•Currently on maximal dose of therapeutic anticoagulation for thromboembolic disease.

Arms & Interventions

1

Intervention: bevacizumab

1

Intervention: erlotinib

Outcomes

Primary Outcomes

Objective response rate

Time Frame: 12 months after treatment initiation (estimated average)

Defined as a proportion of complete response (CR) + partial response (PR) according to RECIST v1.1, the fraction with a response (CR+PR) will be reported separately by cohort, along with a 95% confidence interval

Secondary Outcomes

Overall survival (OS)(Time from study treatment initiation until death from any cause, assessed up to 2 years from study enrollment (estimated average))
Progression-free survival(Time from study treatment initiation until disease progression or death, assessed up to 1 years from study enrollment (estimated average)12 months after treatment initiation (estimated average))
Incidence of adverse events(Time from study treatment initiation up to 30 days after last treatment, 12 months after treatment initiation (estimated average))