Solid TumorsPhase 2BRISKNCT05904457
A Phase II Stydy of Bevacizumab Plus Erlotinib in Patients for Krebs Cycle Altered Cancer
A Phase 2 study testing bevacizumab and erlotinib in people with Solid Tumors and Advanced Solid Tumors, run by Asan Medical Center at 10 sites in South Korea.
Trial 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 Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Solid Tumors, Advanced Solid Tumors, Metastatic Cancer
- What is being tested?
- bevacizumab and erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 10 sitesSouth Korea
- Study dates
- 2 Jan 2023to 31 Jan 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Platelet >= 100,000/mm3
- Hemoglobin >= 9 g/dL Liver function tests
- Total bilirubin ≤ 1.5 xULN
- AST, ALT ≤ 3 xULN (in case of liver metastasis, 5 x upper limit of normal) Renal function tests
- Creatinine clearance >= 30 mL/min
- Life expectancy more than 3 months
- Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
Who cannot join
- 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
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- History of bleeding diathesis or coagulopathy
- Urine dipstick proteinuria≥2+ or urine protein/creatinine ratio >1.0. 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.
- Clinically significant bleeding (hemoptysis, melena, hematochezia, tumor bleeding, etc.), or at risk of significant bleeding (tumor infiltrating into the great vessels or an evident cavitation of cancer lesions)
- Have any of the following gastrointestinal disturbances.
- Unable to take internal medications ② Required intravenous feeding ③ Have malabsorption due to surgical treatment (such as gastrointestinal resection) or underlying disease ④ Have an active peptic ulcer (enrollment is permitted if the patient is being given prophylactic treatment for a previous condition or treatment for complications from gastritis, etc.) ⑤ History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess ≤ 6 months prior to screening
- Serious non-healing wound, ulcer, bone fracture or have undergone a major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to screening.
- Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, or in situ carcinoma of cervix uteri or prostate cancer and curatively treated thyroid cancer of any stage.
- Pregnancy or breast feeding
- Men or women who are not intending to use contraceptive methods during the study period.
- Major surgery is scheduled during the study period
- Other severe acute or chronic medical or psychiatric condition
- Individuals who are deemed to be unsuitable for participation in this study by the investigators for any other reason
- Where participation in this clinical trial is not appropriate in the judgment of the investigator for any other reason
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
South Korea10 sites, 10 recruiting
- Recruiting
Chungnam National University Hospital
Daejeon, Chungcheongnam-do, 35015
Hye-won Ryu
- Recruiting
Gachon University Gil Medical Center
Incheon, 21565
Joo-Hwan Park
- Recruiting
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, 52727
Jung Hoon Kang
- Recruiting
Cha University Bundang Medical Center
Seongnam-si, Gyeonggi-do, 13496
Beo-Deul Kang
- Recruiting
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Jee Hyun Kim
- Recruiting
Korea University Anam Hospital
Seoul, 02841
Ju Won Kim
- Recruiting
Yonsei Cancer Hospital
Seoul, 03722
Min-Kyu Jung
- Recruiting
Asan Medical Center
Seoul, 05505
Inkeun Park
- Recruiting
The Catholic University of Korea, Seoul ST. Mary's Hospital
Seoul, 06591
Se-Jun Park
- Recruiting
Ulsan University Hospital
Ulsan, 44033
Hyeon-Su Im
About this study
Official title: A Phase II Clinical Trial of Bevacizumab Plus eRlotinIb in patientS With Advanced Cancer Having Genetic Alterations in Krebs Cycle (BRISK, KCSG AL22-16)
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
Read the 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.
- Conditions
- Solid Tumors, Advanced Solid Tumors, Metastatic Cancer
- Being tested
- bevacizumab, erlotinib
- Keywords
- Krebs cycle, FH, IDH, SDH, bevacizumab, erlotinib, cancer, aerobic glycolysis, brisk
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
Also called onbevzi
Patients will receive bevacizumab 10 mg/kg IV over 30-90 minutes every 2 weeks until disease progression or unacceptable toxicity.
erlotinibDrug
Also called eltinib
Patients will receive elrotinib 150 mg orally once a day continuously until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: bevacizumab; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
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
Measured: 12 months after treatment initiation (estimated average)
Secondary outcomes (3)
Progression-free survival
Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, PFS will be determined using the Kaplan-Meier method, and the curves presented along with a 95% confidence interval on the median PFS
Measured: 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)
Overall survival (OS)
The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median OS
Measured: Time from study treatment initiation until death from any cause, assessed up to 2 years from study enrollment (estimated average)
Incidence of adverse events
Severity of adverse events will be graded by NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v5.0
Measured: Time from study treatment initiation up to 30 days after last treatment, 12 months after treatment initiation (estimated average)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start2 Jan 2023
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Korean Cancer Study Group, Boryung Pharmaceutical Co., Ltd
- Responsible party
- Principal investigator, Inkeun Park, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05904457
- Sponsor's protocol ID
- KCT0007840
- Acronym
- BRISK
- Status last verified
- Jun 2023
- First submitted
- 6 Jun 2023
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Bevacizumab Plus eRlotinIb in patientS With Advanced Cancer Having Genetic Alterations in Krebs Cycle (BRISK, KCSG AL22-16)
- ClinicalTrials.gov ID
- NCT05904457
- Acronym / sponsor ID
- BRISK / KCT0007840
- Conditions
- Solid Tumors, Advanced Solid Tumors, Metastatic Cancer
- Keywords
- Krebs cycle, FH, IDH, SDH, bevacizumab, erlotinib, cancer, aerobic glycolysis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- Korean Cancer Study Group, Boryung Pharmaceutical Co., Ltd
- Study start
- 2 Jan 2023 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: bevacizumab, Drug: erlotinib |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumabAlso: onbevziPatients will receive bevacizumab 10 mg/kg IV over 30-90 minutes every 2 weeks until disease progression or unacceptable toxicity. | Drug | 1 |
| erlotinibAlso: eltinibPatients will receive elrotinib 150 mg orally once a day continuously until disease progression or unacceptable toxicity. | Drug | 1 |
Primary outcome
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
3 secondary outcomes
Progression-free survival
Time frame: 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)
Overall survival (OS)
Time frame: Time from study treatment initiation until death from any cause, assessed up to 2 years from study enrollment (estimated average)
Incidence of adverse events
Time frame: Time from study treatment initiation up to 30 days after last treatment, 12 months after treatment initiation (estimated average)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
Related trials for Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab and erlotinib in people with Solid Tumors and Advanced Solid Tumors, run by Asan Medical Center at 10 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Inkeun Park, M.D, Ph.D (+82-2-3010-3266, ikpark@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: 12 months after treatment initiation (estimated average)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.