NCT04181060ClinicalTrials.gov
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Randomized Phase III Study of Combination Osimertinib (AZD9291) and Bevacizumab Versus Osimertinib (AZD9291) Alone as First-Line Treatment for Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)
باختصار
This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene…
المرحلة 3مطلوب 300 مشارك603 مواقعدولة واحدة
الفئات
مسجَّلة في سجل واحد
- ClinicalTrials.govNCT04181060فتح هذا السجل في ClinicalTrials.govتمت المزامنة قبل أسبوعين
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How this study is set up
The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.
- Present: Registered before enrolment beganFirst posted 2019-11-29; recorded start 2020-12-28
- Present: Has a defined primary outcomeA primary outcome measure is listed in the record
- Present: The primary outcome states a time frameThe primary outcome measure records a time frame
- Present: Participants are randomly assignedAllocation is recorded as randomised
- Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
- Not stated: Open label (no blinding)Masking is recorded as none (open label)
- Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
- Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
- Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
- Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
- Present: Sponsor has 1548 other studies in this databaseCounted from the lead sponsor named in the record (National Cancer Institute (NCI))
- Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database
- The record lists 5 conditions.
- Lead sponsor type recorded as: US National Institutes of Health.
- Intervention regulatory context: investigational, within a phased regulatory pathway.
Trial stature
Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.
A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.
How this score is built
- Randomised allocation20/20
Participants are randomly allocated between arms
- Blinding0/20
Open-label
- Control arm15/15
Active-comparator control arm
- Primary-outcome specificity10/10
Named primary outcome with a defined time frame
- Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
- Multi-centre8/8
Multi-centre: 604 sites
- Data monitoring committee0/7
No data monitoring committee stated
- Prospective registration5/5
Registered before the study start date
- Protocol / SAP posted0/5
No protocol or SAP posted to the registry
A medium-sized study: 300 participants (target), run at 603 sites.
How this score is built
- Enrolment24/40
300 participants (target)
- Site count25/25
604 sites
- Country count0/15
Single country
- Planned duration10/10
Planned over about 73 months
- Sponsor scale10/10
National Cancer Institute (NCI) has led 1,534 trials in our corpus
We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.
How this score is built
- Investigator standing0/100
No investigator recorded in the registry for this trial
These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.
ملخص
This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.
الحالات
- Advanced Lung Non-Squamous Non-Small Cell Carcinoma
- Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
- Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
- Stage IIIB Lung Cancer AJCC v8
- Stage IV Lung Cancer AJCC v8
الأهلية
| الجنس | الجميع |
|---|---|
| الأعمار | 18 Years – لا حد أقصى |
| المتطوعون الأصحّاء | لا |
الأهلية كما كُتبت في السجل
الأهلية في عبارات بسيطة
لم تُقسَّم معايير هذا السجل إلى عبارات منفصلة بعد. نص السجل أعلاه كامل وهو النسخة المُعتمَدة.
تصميم الدراسة
| نوع الدراسة | تدخّلية |
|---|---|
| المرحلة | المرحلة 3 |
| التخصيص | معشّاة |
| نموذج التدخّل | PARALLEL |
| الغرض الأساسي | TREATMENT |
| التعمية | NONE (0) |
| التجنيد | مطلوب 300 مشارك |
الجهة الراعية والمتعاونون
- National Cancer Institute (NCI) الجهة الراعية
الأذرع والتدخلات
- Arm A (osimertinib)ACTIVE_COMPARATOR
Patients receive osimertinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.
- Arm B (osimertinib, bevacizumab)EXPERIMENTAL
Patients receive osimertinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.
التدخلات
- منتج بيولوجي Bevacizumab
Given IV
- إجراء Biospecimen Collection
Undergo blood and urine sample collection
- إجراء Computed Tomography
Undergo CT
- إجراء Echocardiography Test
Undergo ECHO
- إجراء Magnetic Resonance Imaging
Undergo MRI
- إجراء Multigated Acquisition Scan
Undergo MUGA
- دواء Osimertinib
Given PO
مقاييس النتائج
مقياس النتيجة الأولي
Progression-free survival (PFS)
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. PFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%.
الإطار الزمني From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 10 years
مقياس النتيجة الثانوي
Overall survival (OS)
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. OS will be tested at the one-sided 10% level.
الإطار الزمني From randomization to death from any cause, assessed up to 10 years
مقياس النتيجة الثانوي
Best objective response rate
Best objective response will be evaluated via RECIST 1.1 criteria. Will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
الإطار الزمني Up to 10 years
مقياس النتيجة الثانوي
Time to central nervous system progression
Will be estimated using competing risks methodology, adjusting for death and progression as competing events. Regular central nervous system imaging will occur when patients are on treatment. After they discontinue study treatment, central nervous system imaging will be symptom-prompted during follow up.
الإطار الزمني From study randomization to evidence of central nervous system progressive disease, with death and progression as competing events, assessed up to 10 years
مقياس النتيجة الثانوي
Central nervous system progression-free survival
Will be estimated using the Kaplan-Meier method.
الإطار الزمني From study randomization to evidence of central nervous system progressive disease or death from any cause, whichever occurs first, assessed up to 10 years
مقياس النتيجة الثانوي
Incidence of adverse events
Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE). Will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
الإطار الزمني Up to 30 days after the last administration of investigational agent
مقياس نتيجة آخر
Mechanisms of resistance to AZD9291 (osimertinib) and AZD9291 (osimertinib) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA)
Preliminary analyses of these data will utilize tests for association comparing the frequency of a particular genomic aberration at baseline and at progression (for example, using McNemar's test) and association between alterations and baseline characteristics (for example, using Fisher's exact test). More sophisticated analyses may include multivariable logistic regression modeling and/or competing risks analysis.
الإطار الزمني Up to 10 years
مقياس نتيجة آخر
Circulating tumor deoxyribonucleic acid (ctDNA) clearance on study treatment
Will assess ctDNA clearance on study treatment and associate ctDNA clearance with clinical outcomes. Cox regression analysis will be used to assess whether EGFR ctDNA clearance is an independent predictor for PFS (and OS), adjusted by treatment effect, the presence of brain metastasis (yes versus \[vs.\] no), EGFR exon 19 deletion/L858R vs other, Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs 2) and other possible clinical and biological risk factors.
الإطار الزمني Up to 10 years
التواريخ
| تاريخ البدء | 28 ديسمبر 2020 (فعلي) |
|---|---|
| الإتمام الأولي | 31 ديسمبر 2026 (تقديري) |
| الإتمام | 31 ديسمبر 2026 (تقديري) |
| أول نشر | 29 نوفمبر 2019 (فعلي) |
| آخر تحديث | 10 سبتمبر 2026 |
| النتائج منشورة | غير مذكور في سجل السجل |
| آخر تأكيد للحالة | مايو 2026 |
فعلي يعني أن الحدث وقع. تقديري يعني أن الجهة الراعية تتوقعه. للكلمتين معنيان مختلفان.
المواقع
326 موقعاً قيد التجنيد
United States
| المنشأة | المدينة | الولاية أو المنطقة | الحالة |
|---|---|---|---|
| Providence Regional Cancer System-Aberdeen | Aberdeen | Washington | مُعلَّق |
| Hickman Cancer Center | Adrian | Michigan | مُعلَّق |
| New Mexico Oncology Hematology Consultants | Albuquerque | New Mexico | مُعلَّق |
| University of New Mexico Cancer Center | Albuquerque | New Mexico | قيد التجنيد |
| Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | قيد التجنيد |
| OSF Saint Anthony's Health Center | Alton | Illinois | مُعلَّق |
| Mary Greeley Medical Center | Ames | Iowa | قيد التجنيد |
| McFarland Clinic - Ames | Ames | Iowa | قيد التجنيد |
| Community Hospital of Anaconda | Anaconda | Montana | قيد التجنيد |
| Alaska Women's Cancer Care | Anchorage | Alaska | مُعلَّق |
| Anchorage Oncology Centre | Anchorage | Alaska | مُعلَّق |
| Katmai Oncology Group | Anchorage | Alaska | قيد التجنيد |
| Providence Alaska Medical Center | Anchorage | Alaska | مُعلَّق |
| Alaska Breast Care and Surgery LLC | Anchorage | Alaska | مُعلَّق |
| Anchorage Radiation Therapy Center | Anchorage | Alaska | مُعلَّق |
| Anchorage Associates in Radiation Medicine | Anchorage | Alaska | مُعلَّق |
| Alaska Oncology and Hematology LLC | Anchorage | Alaska | قيد التجنيد |
| UI Health Care Mission Cancer and Blood - Ankeny Clinic | Ankeny | Iowa | قيد التجنيد |
| Trinity Health Saint Joseph Mercy Hospital Ann Arbor | Ann Arbor | Michigan | قيد التجنيد |
| Kaiser Permanente-Deer Valley Medical Center | Antioch | California | قيد التجنيد |
| ThedaCare Regional Cancer Center | Appleton | Wisconsin | قيد التجنيد |
| Mission Hope Medical Oncology - Arroyo Grande | Arroyo Grande | California | مُعلَّق |
| Emory University Hospital Midtown | Atlanta | Georgia | قيد التجنيد |
| Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | قيد التجنيد |
| The Medical Center of Aurora | Aurora | Colorado | مُعلَّق |
| Rush-Copley Medical Center | Aurora | Illinois | قيد التجنيد |
| Rocky Mountain Cancer Centers-Aurora | Aurora | Colorado | قيد التجنيد |
| UH Seidman Cancer Center at UH Avon Health Center | Avon | Ohio | قيد التجنيد |
| Saint Alphonsus Cancer Care Center-Baker City | Baker City | Oregon | مُعلَّق |
| Mercy Oncology and Hematology - Clayton-Clarkson | Ballwin | Missouri | مُعلَّق |
| CommonSpirit Saint Joseph Hospital - Bardstown | Bardstown | Kentucky | مُعلَّق |
| Memorial Sloan Kettering Basking Ridge | Basking Ridge | New Jersey | قيد التجنيد |
| Houston Methodist San Jacinto Hospital | Baytown | Texas | قيد التجنيد |
| UHHS-Chagrin Highlands Medical Center | Beachwood | Ohio | قيد التجنيد |
| Indu and Raj Soin Medical Center | Beavercreek | Ohio | مُعلَّق |
| PeaceHealth Saint Joseph Medical Center | Bellingham | Washington | مُعلَّق |
| Strecker Cancer Center-Belpre | Belpre | Ohio | قيد التجنيد |
| Sanford Joe Lueken Cancer Center | Bemidji | Minnesota | نشط، دون تجنيد |
| Saint Charles Health System | Bend | Oregon | قيد التجنيد |
| ThedaCare Cancer Care - Berlin | Berlin | Wisconsin | قيد التجنيد |
| Walter Reed National Military Medical Center | Bethesda | Maryland | مُعلَّق |
| Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | قيد التجنيد |
| Beverly Hospital | Beverly | Massachusetts | نشط، دون تجنيد |
| Billings Clinic Cancer Center | Billings | Montana | قيد التجنيد |
| Sanford Bismarck Medical Center | Bismarck | North Dakota | نشط، دون تجنيد |
| Illinois CancerCare-Bloomington | Bloomington | Illinois | قيد التجنيد |
| Saint Elizabeth Boardman Hospital | Boardman | Ohio | مُعلَّق |
| Saint Alphonsus Cancer Care Center-Boise | Boise | Idaho | قيد التجنيد |
| Saint Luke's Cancer Institute - Boise | Boise | Idaho | قيد التجنيد |
| Central Care Cancer Center - Bolivar | Bolivar | Missouri | مُعلَّق |
يُدرَج 553 موقعاً إضافياً في سجل السجل.
مستندات الدراسة
لا تُرتبط أي مستندات في سجل السجل هذا.
التغيّرات عبر الزمن
- 5 أغسطس 2026
أُزيل موقع
1 site removed (603 total)
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