Osimertinib Plus Bevacizumab in Untreated EGFR Exon21 L858R Mutated NSCLC

NCT04988607 | Unknown Phase 2

• 1 other identifier: CTONG2002
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, randomized, open label study to investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib montherapy in treatment-naïve recurrent or metastatic NSCLC patients harbouring EGFR exon 21 L858R mutation.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of osimertinib plus bevacizumab treatment compared with osimertinib monotherapy

  Progression free survival (PFS) by Investigator assessment as defined by RECIST 1.1

  up to 3 years after the first patient is randomized

Secondary Outcomes (13)

• OS rate at 24 months

  the Kaplan-Meier estimate of OS at 24 months

• TTime to treatment failure (TTF)

  up to 3 years after the first patient is randomized

• Objective Response Rate (ORR)

  up to 3 years after the first patient is randomized

• Disease Control Rate (DCR)

  up to 3 years after the first patient is randomized

• Duration of Response (DoR)

  up to 3 years after the first patient is randomized

Study Arms (2)

osimertinib plus bevacizumab

EXPERIMENTAL

Osimertinib 80 mg (QD) in combination with Bevacizumab (15 mg/kg) (Q3W)

Drug: Osimertinib; Drug: Bevacizumab

osimertinib

ACTIVE COMPARATOR

All patients randomized into this will only receive Osimertinib 80mg (QD)

Drug: Osimertinib

Interventions

Osimertinib DRUG

osimertinib plus bevacizumab arm is dosed at osimertinib 80 mg orally once every day combined with bevacizumab 15mg/kg by intravenous drip infusion on day 1 of a 21-day (within 3 days) cycle

Also known as: AZD9291, Tagrisso

osimertinib plus bevacizumab

Bevacizumab DRUG

osimertinib plus bevacizumab arm is dosed at osimertinib 80 mg orally once every day combined with bevacizumab 15mg/kg by intravenous drip infusion on day 1 of a

Also known as: Avastin

osimertinib plus bevacizumab

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses.
• Male or female, age ≥18 years old.
• Newly diagnosed metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer \[IASLC\] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy.
• Histologically or cytologically documented non-squamous NSCLC
• Documented EGFR exon 21 L858R mutation
• ECOG performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks
• Life expectancy ≥12 weeks at Day 1.
• At least 1 measurable extracranial lesion according to RECIST 1.1; (Note: ① At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI). ② CT/MRI scan slice thickness/interval no greater than 5 mm. ③ 10 mm caliper measurement by clinical examination (lesions that cannot be accurately measured with calipers should be recorded as nonmeasurable) ④ If brain metastases were received radiotherapy, these brain metastasis can't be as target lesions).
• Patients with CNS metastases whose condition was neurologically stable 2 weeks (after steroids treatment or non-treatment) will be allowed, including leptomeningeal metastases
• Patients who have undergone radiotherapy may be enrolled if the participants meet the following conditions • The patient has no history of radiotherapy for lesions in lung fields within 28 days before the randomization.
• For radiotherapy outside the chest region, at least 28 days have elapsed by the time of randomization since the final irradiation date. (if the radiotherapy given as palliation to bone metastases within 2 weeks, the patient should recovery from all toxicities)
• Adequate haematological function:
• Absolute neutrophil count (ANC)≥1.5×109/L\* AND
• Platelet count≥100×109/L\* AND

You may not qualify if:

• Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD 3. History or evidence of inherited bleeding diathesis or coagulopathy that increases the risk of bleeding.
• \. Uncontrolled hypertension (blood pressures: systolic\>150 mmHg and/or diastolic \>100 mmHg).
• \. Prior history of hypertensive crisis or hypertensive encephalopathy. 6. Significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• \. Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value;
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; eg, complete left bundle branch block, third-degree heart block, second-degree heart block;
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium\*, magnesium\* and calcium\* below the lower limit of normal (LLN), heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
• Levels must be in the normal range prior to first administration of osimertinib.
• \. Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent.
• \. Any unresolved toxicities from prior systemic therapy (eg, adjuvant chemotherapy) greater than CTCAE Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
• \. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib 11. History of haemoptysis, defined as \> 2.5 ml of red blood per event within 3 months prior to randomization.
• \. History of haemoptysis, defined as \> 2.5 ml of red blood per event within 3 months prior to randomization.
• \. Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g., pulmonary artery or superior vena cava).
• \. Non-healing wound, active peptic ulcer, or bone fracture 14. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrolment.
• \. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrolment.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib; Bevacizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yi Long Wu, Doctor

CONTACT

13809775415; syylwu@live.cn

Qing Zhou, Ph.D

CONTACT

13544561166; gzzhouqing@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 1:1, the experimental arm is osimertinib plus bevacizumab, while the control arm is osimertinib monotherapy

Study Record Dates

• First Submitted: June 20, 2021
• First Posted: August 3, 2021
• Study Start: August 1, 2021
• Primary Completion: November 1, 2024
• Study Completion: May 1, 2025
• Last Updated: August 3, 2021

Record last verified: 2021-04

Locations

CN (1)