A Phase II Stydy of Bevacizumab Plus Erlotinib in Patients for Krebs Cycle Altered Cancer

NCT05904457 | Unknown Phase 2

• 1 other identifier: KCT0007840
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 10

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

Conditions

Solid Tumors; Advanced Solid Tumors; Metastatic Cancer

Keywords

Krebs cycle; FH; IDH; SDH; bevacizumab; erlotinib; cancer; aerobic glycolysis; brisk

Outcome Measures

Primary Outcomes (1)

• 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

  12 months after treatment initiation (estimated average)

Secondary Outcomes (3)

• 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)

• Overall survival (OS)

  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 from study treatment initiation up to 30 days after last treatment, 12 months after treatment initiation (estimated average)

Study Arms (1)

1

EXPERIMENTAL

Drug: bevacizumab; Drug: erlotinib

Interventions

bevacizumab DRUG

Patients will receive bevacizumab 10 mg/kg IV over 30-90 minutes every 2 weeks until disease progression or unacceptable toxicity.

Also known as: onbevzi

1

erlotinib DRUG

Patients will receive elrotinib 150 mg orally once a day continuously until disease progression or unacceptable toxicity.

Also known as: eltinib

1

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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 \>1.0. 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.

Sponsors & Collaborators

• Asan Medical Center: lead
• Korean Cancer Study Group: collaborator
• Boryung Pharmaceutical Co., Ltd: collaborator

Study Sites (10)

Chungnam National University Hospital

Daejeon, Chungcheongnam-do, 35015, South Korea

RECRUITING

Cha University Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, 52727, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

Yonsei Cancer Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

The Catholic University of Korea, Seoul ST. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Ulsan University Hospital

Ulsan, 44033, South Korea

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Inkeun Park, M.D, Ph.D

CONTACT

+82-2-3010-3266; ikpark@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 15, 2023
• Study Start: January 2, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2026
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

KR (10)