Trial Title:
Study of Osimertinib+Bevacizumab+Chemotherapy for EGFR+ Advanced Non-Small Cell Lung Cancer With Concurrent Mutations
NCT ID:
NCT05507606
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Bevacizumab
Carboplatin
Pemetrexed
Osimertinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Osimertinib
Description:
osimertinib 80mg/d
Arm group label:
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Other name:
EGFR-TKI
Intervention type:
Drug
Intervention name:
Bevacizumab Biosimilar IBI305
Description:
Bevacizumab, 7.5mg/kg d1; was discontinued after 2 years
Arm group label:
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Other name:
Anti-angiogenesis
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin AUC5, d1; was stopped after 4 cycles
Arm group label:
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Other name:
Chemotherapy
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed, 500mg/m2, d1;Q3W/cycle; was discontinued after 2 years
Arm group label:
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Other name:
Chemotherapy
Summary:
This is a single-center, open-label, phase I clinical trial aimed to evaluate the
efficacy and safety of Osimertinib+Bevacizumab+Carboplatin and Pemetrexed for Untreated
Patients With EGFR Mutation Advanced Non-squamous Non-Small Cell Lung Cancer With
Concomitant Mutations.
Detailed description:
Patients received Bevacizumab, 7.5mg/kg d1, Pemetrexed, 500mg/m2, d1 and Carboplatin
AUC5, d1; osimertinib 80mg/d , d1-21, Q3W/cycle; induction therapy for 4 cycle, then
Carboplatin was stopped after 4 cycles, and osimertinib combined with bevacizumab and
pemetrexed were given for maintenance treatment every 3 weeks; Bevacizumab and pemetrexed
were discontinued for 2 years; After that, the maintenance treatment of osimertinib was
continued
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects who must meet all the following criteria should be selected:
1. Agree to participate in this trial and sign written informed consent form.
2. Male or female, age between 18 and 70 years.
3. Expected survival time ≥ 3 months and able to be followed-up.
4. Stage IIIB/IIIC/IV non-squamous NSCLC patients without previous systemic therapy
(according to AJCC8th) or patients with stage IIIB/IIIC/IV non-squamous NSCLC who
have relapsed after surgery (if adjuvant therapy was administered, more than 6
months of drug discontinuation is required).
5. The tumor harbors epidermal growth factor receptor (EGFR) mutations(include 19del,
L858R, T790M, G719X, L861Q, S768I, 20 A763-Y764ins), and at least concurrent with
TP53
6. Patients can not receive concurrent chemoradiothrapy after multidisciplinary
consultation and discussion.
7. At least one measurable tumor indicator along with a lesion with a maximum diameter
of ≥ 1 cm (diagnosed by imaging, e.g., CT, MRI, ECT).
8. ECOG PS 0-1 within 7 days before enrollment.
9. Within 14 days prior to the start of treatment, laboratory results of routine blood,
liver and kidney function and hormone levels meet the following criteria: white
blood cell(WBC) ≥3.5× 109/L, platelets (PLT) ≥ 80 × 109/L, neutrophils (ANC) ≥ 1.5 ×
109/L, hemoglobin (HGB) ≥ 80 g/L, aspartate aminotransferase (AST) ≤ 2.5 × upper
limit of normal (ULN) (≤ 5 × ULN for liver metastases), alanine aminotransferase
(ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 ×
ULN, and alanine aminotransferase (ALT) ≤ 1.5 × ULN. × ULN), alanine
aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin
(TIBC) ≤ 1.5 × ULN, serum creatinine (CR) ≤ 1.25 × ULN; cortisol and thyroid
function are in the normal range.
10. Toxic effects of prior chemotherapy have resolved to grade 1 or less (except
alopecia). Subjects must have recovered from toxicity or complications of these
interventions if they have received major surgical treatment or > 30Gy of radiation
therapy, i.e., they are still eligible for enrollment after 6 months.
Exclusion Criteria:
Subjects who meet any of the following criteria could not participate in this study:
1. non-squamous NSCLC just harbors EGFR mutations
2. Prior treatment with first,second and 3rd EGFR-TKI.
3. Received bevacizumab and/or pemetrexed within 6 months prior to the first dose of
study drug.
4. Prior treatment with PD-1/PD-L1 antibodies within 3 months prior to the first dose
of study drug.
5. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule
therapy, or major surgical procedure within 1 month prior to the first use of study
drug; received chest radiation therapy greater than 30 Gy within 6 months prior to
the first use of study drug; received chest radiation therapy at 30 Gy or less
within 1 month prior to the first use of study drug.
6. Participating or have participated in investigational drug therapy within 4 weeks
prior to the first dose of the trial.
7. Other malignant tumors with disease progression or requiring aggressive treatment
within 5 years of enrollment. Exceptions included early-stage tumors (carcinoma in
situ or stage I tumors) that received radical treatment, basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or
carcinoma in situ of the breast that received potentially radical treatment.
8. Having congenital or acquired immune deficiency (e.g., HIV-infected patients),
active hepatitis B (HBV-DNA ≥10^3 copies/ml), or hepatitis C (positive for hepatitis
C antibodies and HCV-RNA above the lower limit of detection for the assay).
9. Patients who have received live vaccine within 4 weeks prior to the first
administration of study drug are permitted to receive inactivated viral.
10. Patients with known active central nervous system (CNS) metastases and/or cancerous
meningitis. Subjects who have had treatment for brain metastases may also
participate in this study provided that the subject is stable (no evidence of
progression for at least 4 weeks and all neurological symptoms have returned to
baseline levels as determined by MRI prior to the first dose), has no evidence of
new or expanding brain metastases, and has not used hormone therapy for at least 3
days prior to study dosing.
11. Bleeding tendency, high bleeding risk, or coagulopathy with a history of thrombotic
disease within 6 months and/or hemoptysis within 3 months; being treated with full
doses of oral and/or parenteral anticoagulants and thrombolytics (prophylactic
anticoagulation is allowed); having used aspirin or other non-steroidal
anti-inflammatory drugs that inhibit platelet function within 10 days; and CT/MRI
imaging showing tumor encapsulation or invasion of the lumen of large blood vessels.
12. Poorly controlled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) and
patients with prior hypertensive crisis and hypertensive encephalopathy; severe
cerebrovascular disease.
13. Non-healing wounds, peptic ulcers in active phase, tracheo-esophageal fistulas,
gastrointestinal perforations and intra-abdominal abscesses within 6 months.
14. Have an active infection that requires systemic treatment via Intravenous injection.
15. Have mental illness or other condition, such as uncontrolled heart or lung disease,
diabetes mellitus, etc., that prevents cooperation with study treatment and
monitoring requirements.
16. Known allergy to any of the components of the study drug.
17. Patients who are regular users of any drug (including "recreational" use) or have
recent history (within 1 year) of substance abuse (including alcohol) when signing
the informed consent form.
18. Pregnancy or breast feeding.
19. Poor compliance and inability to cooperate with the clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Contact:
Last name:
Liang MD Liu, Ph.D
Phone:
86-22-23340123
Phone ext:
3172
Email:
liangcoh@163.com
Contact backup:
Last name:
Xiubao MD Ren, Ph.D
Phone:
86-22-23340123
Phone ext:
3173
Email:
renxiubao@tjmuch.com
Start date:
August 1, 2021
Completion date:
August 1, 2024
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05507606