Compare Bevacizumab in Combination With Erlotinib Versus Erlotinib Alone in NSCLC Patients Activating EGFR Mutations

NCT02759614 | Completed Phase 3 DMC

• 1 other identifier: CTONG1509
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, controlled, multicenter, Phase III study. Patients will be randomly assigned to treatment group (1:1) through a dynamic randomization process with use of the following stratification factors: sex (female/male), disease stage (stage IIIb vs. stage IV vs. recurrence), and EGFR gene mutation (exon 19 deletion vs. exon 21 L858R).

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) by IRC

  To evaluate the efficacy of bevacizumab combined with erlotinib compared with erlotinib alone in patients with NSCLC harbouring activating EGFR mutations, as measured by independent review committee assessed progression-free survival using RECIST v1.1

  The primary PFS analysis will be performed when approximately 224 PFS events (disease progression or death, whichever occurs first) have occurred, which is estimated to occur at approximately 18 months after enrollment of the last patient.

Secondary Outcomes (8)

• Progression-free survival (PFS) by investigator using RECIST v1.1

  The primary PFS analysis will be performed when approximately 224 PFS events (disease progression or death, whichever occurs first) have occurred, which is estimated to occur at approximately 18 months after enrollment of the last patient.

• Objective response rate (ORR) by IRC using RECIST v1.1

  baseline overall tumor assessment can be performed up to 28 days prior to randomization. Post-baseline assessment will be performed every six weeks until 1st disease progression, through study completion, an average of 2 years.

• Objective response rate (ORR) by investigator using RECIST v1.1

  baseline overall tumor assessment can be performed up to 28 days prior to randomization. Post-baseline assessment will be performed every six weeks until 1st disease progression, through study completion, an average of 2 years.

• Disease control rate (DCR) by IRC using RECIST v1.1

  That is expected to be approximately 57 months.

• Disease control rate (DCR) by investigator using RECIST v1.1

  That is expected to be approximately 57 months.

Study Arms (2)

Bevacizumab and Erlotinib

EXPERIMENTAL

Bevacizumab 15 mg/kg shall be intravenous infusion on day 1 once every 3 weeks, Erlotinib 150 mg tablets shall be administered orally every day at least one hour before or two hours after the ingestion of food.

Drug: Bevacizumab; Drug: Erlotinib

Erlotinib

ACTIVE COMPARATOR

Erlotinib 150 mg tablets shall be administered orally every day at least one hour before or two hours after the ingestion of food.

Drug: Erlotinib

Interventions

Bevacizumab DRUG

Bevacizumab15mg/kg by intravenous drip infusion on day 1 of a 21-day (within 3 days) cycle and Erlotinib orally once daily at 150mg/day

Also known as: Avastin

Bevacizumab and Erlotinib

Erlotinib DRUG

Erlotinib 150mg, orally once a day

Also known as: Tarceva

Bevacizumab and Erlotinib; Erlotinib

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria for study entry:
• Signed Informed Consent Form.
• Age≥18 years.
• Able to comply with the study protocol, in the investigator's judgment.
• Histologically or cytologically documented inoperable, locally advanced (Stage IIIb who are not amenable for combined modality treatment), metastatic (Stage IV) or recurrent non-squamous NSCLC. Diagnoses of non-squamous NSCLC based on sputum cytology alone are not acceptable.
• An exon 19 deletion mutation or exon 21 L858R mutation has been found in high-sensitivity EGFR mutation tests by PCR using tumor tissue centrally confirmed. Direct sequencing is not accepted.
• Eastern Cooperative Oncology Group performance status 0-1.
• Life expectancy≥12 weeks.
• Previous systemic cytotoxic chemotherapy for locally advanced, metastatic or recurrent disease has not been performed. Subjects who have undergone intracavity administration with an antineoplastic agent during pleurodesis are not permitted. For patients who have undergone pre- or postoperative adjuvant chemotherapy, at least 6 months have elapsed since the final administration date.
• Patients who have undergone radiotherapy may be enrolled if they 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)
• Measurable disease at baseline. At least one lesion is present that can be measured in accordance with the criteria in Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. However, sites treated by radiotherapy should not be considered measurable.
• Adequate haematological function:
• Absolute neutrophil count (ANC)≥1.5×109/L AND

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Mixed adenosquamous carcinomas with predominantly squamous component.
• A positive result for the exon 20 T790M mutation from any high-sensitivity EGFR mutation test such as digital PCR using tumor tissue or cells.
• Evidence of CNS metastases, except for the patients without any symptom or the patients with symptom but have stable disease for at least 28 days after treatment of CNS metastases.
• 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).
• Major surgery (including open biopsy) or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during study treatment.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device are excluded within 7 days prior to initiation of study treatment. Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
• Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (325 mg/day) or other nonsteroidal anti-inflammatory agents known to inhibit platelet function.
• Current or recent (within 10 days of first dose of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed.
• 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.
• Clinically significant (i.e., active) cardiovascular disease, including but not limited to cerebral vascular accident (CVA) or (transient ischemic attack) TIA (≤6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, congestive heart failure New York Heart Association Class≥II, or serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment or not controlled by medication.
• Significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Guangzhou, Guangdong, 510080, China

Location

Related Publications (3)

• Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.

  PMID: 23816960 RESULT

• Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.

  PMID: 25175099 RESULT

• Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.

  PMID: 20573926 RESULT

MeSH Terms

Interventions

Bevacizumab; Erlotinib Hydrochloride

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

Study Officials

• Qing Zhou, PhD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: May 3, 2016
• Study Start: April 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: March 30, 2020
• Last Updated: March 13, 2026

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)