Trial Title:
A Phase II Stydy of Bevacizumab Plus Erlotinib in Patients for Krebs Cycle Altered Cancer
NCT ID:
NCT05904457
Condition:
Solid Tumors
Advanced Solid Tumors
Metastatic Cancer
Conditions: Official terms:
Neoplasms
Neoplasm Metastasis
Bevacizumab
Erlotinib Hydrochloride
Conditions: Keywords:
Krebs cycle
FH
IDH
SDH
bevacizumab
erlotinib
cancer
aerobic glycolysis
brisk
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
bevacizumab
Description:
Patients will receive bevacizumab 10 mg/kg IV over 30-90 minutes every 2 weeks until
disease progression or unacceptable toxicity.
Arm group label:
1
Other name:
onbevzi
Intervention type:
Drug
Intervention name:
erlotinib
Description:
Patients will receive elrotinib 150 mg orally once a day continuously until disease
progression or unacceptable toxicity.
Arm group label:
1
Other name:
eltinib
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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
2. Age 19 or more
3. Histologically confirmed solid cancer
4. 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.
5. Patients with locally advanced, recurrent, or metastatic disease not amenable to
surgery, radiotherapy, or combined modality therapy with curative intent
6. 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
7. Measurable disease according to RECIST v1.1 criteria
8. ECOG performance status 0 or 2
9. 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
10. Life expectancy more than 3 months
11. 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
Exclusion Criteria:
1. 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
2. Previous radiotherapy to the only measurable lesion: but previous radiotherapy will
be permitted unless the lesion is the only measurable lesion
3. 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.
4. 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.
5. Inadequately controlled hypertension (systolic blood pressure > 150 mmHg or
diastolic pressure > 100 mmHg on anti-hypertensive medications).
6. History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6
months prior to screening
7. History of bleeding diathesis or coagulopathy
8. 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.
9. Currently on maximal dose of therapeutic anticoagulation for thromboembolic disease.
10. 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)
11. 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
12. 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.
13. 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.
14. Pregnancy or breast feeding
15. Men or women who are not intending to use contraceptive methods during the study
period.
16. Major surgery is scheduled during the study period
17. Other severe acute or chronic medical or psychiatric condition
18. Individuals who are deemed to be unsuitable for participation in this study by the
investigators for any other reason
19. Where participation in this clinical trial is not appropriate in the judgment of the
investigator for any other reason
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Chungnam National University Hospital
Address:
City:
Daejeon
Zip:
35015
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hye-won Ryu
Facility:
Name:
Cha University Bundang Medical Center
Address:
City:
Seongnam
Zip:
13496
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Beo-Deul Kang
Facility:
Name:
Seoul National University Bundang Hospital
Address:
City:
Seongnam
Zip:
13620
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jee Hyun Kim
Facility:
Name:
Gyeongsang National University Hospital
Address:
City:
Jinju
Zip:
52727
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jung Hoon Kang
Facility:
Name:
Gachon University Gil Medical Center
Address:
City:
Incheon
Zip:
21565
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Joo-Hwan Park
Facility:
Name:
Korea University Anam Hospital
Address:
City:
Seoul
Zip:
02841
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Ju Won Kim
Facility:
Name:
Yonsei Cancer Hospital
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Min-Kyu Jung
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Inkeun Park
Facility:
Name:
The Catholic University of Korea, Seoul ST. Mary's Hospital
Address:
City:
Seoul
Zip:
06591
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Se-Jun Park
Facility:
Name:
Ulsan University Hospital
Address:
City:
Ulsan
Zip:
44033
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hyeon-Su Im
Start date:
January 2, 2023
Completion date:
January 31, 2026
Lead sponsor:
Agency:
Asan Medical Center
Agency class:
Other
Collaborator:
Agency:
Korean Cancer Study Group
Agency class:
Other
Collaborator:
Agency:
Boryung Pharmaceutical Co., Ltd
Agency class:
Industry
Source:
Asan Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05904457
