Non Small Cell Lung CancerPhase 2NCT04099836
Atezolizumab and Bevacizumab in EGFR Mutant NSCLC in Patients With Progressive Disease After Receiving Osimertinib
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Non Small Cell Lung Cancer, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Atezolizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2020to 15 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Histologic documentation of primary lung carcinoma, non-squamous histology with EGFR exon deletion 19 or exon 21 L858R mutation
- Stage IV disease according to the 8th Edition of the American Joint Committee on Cancer staging system
- Disease progression on osimertinib
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 (appendix 1)
- Measureable disease as defined by RECIST 1.1 (appendix 2)
Show all 20Show fewer
- The following laboratory values obtained ≤ 30 days prior to starting study therapy
- ANC ≥ 1, 500 / mm3
- Platelet count, ≥ 100,000 / mm3
- Hemoglobin ≥ 9.0 g / dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Serum Glutamic Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, AST) and Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Aminotransferase, ALT) ≤2.5 x ULN in patients without liver or bone metastases; < 5 x ULN in patients with liver or bone metastases.
- Cockcroft-Gault calculated creatinine clearance of ≥ 45 ml/min (appendix 3) or creatinine ≤1.5 x ULN
- Urine protein/creatinine (UPC) ratio ≤1.
- Negative pregnancy test done ≤7 days (or per institutional policy) prior to start of study therapy, for women of childbearing potential only. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test of must have evidence of non-child bearing potential by fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments;
- Women under 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution;
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- Male subjects should be willing to use barrier contraception.
- Provide informed written consent
Who cannot join
- Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component.
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- Other active malignancy ≤ 2 years prior to study cycle 1 day 1 of study therapy. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or adequately treated stage I or II cancer. NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer.
- History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2), unstable angina pectoris, or ventricular arrhythmia with ≤ 6 months
- History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to study cycle 1 day 1 of study therapy.
- History of bleeding diathesis or coagulopathy.
Show all 19Show fewer
- Inadequately controlled hypertension (systolic blood pressure of >160 mmHg or diastolic pressure >100 mmHg on anti-hypertensive medications). Note: History of hypertensive crisis or hypertensive encephalopathy not allowed.
- Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days or core biopsy ≤ 7 days prior to starting therapy
- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess ≤6 months prior to study cycle 1 day 1 of study therapy.
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
- History of hemoptysis ≥ grade 2 (defined as bright red blood of at least 2.5 mL) ≤ 3 months prior to cycle 1 day 1 of study therapy.
- Symptomatic untreated brain metastases which is defined as persistent neurological symptoms or requiring ongoing use of steroids. Asymptomatic untreated brain metastases are allowed if ≤ 1 cm
- Significant vascular disease (e.g. aortic aneurysm surgical repair or recent peripheral arterial thrombosis) ≤6 months prior to starting study therapy
- Radiotherapy to any site for any reason ≤ 14 days prior to study cycle 1 day 1 of study therapy.
- Pre-existing and clinically active interstitial lung disease
- Autoimmune condition requiring ongoing or intermittent systemic treatment. Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study treatment initiation. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Prior therapy with anti-PD-1 or anti-PD-L1 immunotherapy,
- Prisoners, participants who are involuntarily incarcerated, or participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Single Arm Phase 2 Trial of Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib (TOP 1901)
The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib.
Read the detailed description
This study will be single arm, open label, phase 2 study which will include patients with stage 4 NSCLC patients with EGFR mutations and who have progressed on osimertinib.
Although both atezolizumab and bevacizumab are approved for the treatment of NSCLC, the combination of atezolizumab and bevacizumab has not been approved by the FDA for the treatment of specific non-small cell lung cancer (NSCLC).
Patients who have one of the following EGRF mutations: exon 19 or exon 21 L858R with progressive disease on osimertinib may be eligible to participate in this study. If enrolled into the study, the study team will give the patient atezolizumab (1200 mg) combined with bevacizumab (15 mg/kg) every 3 weeks intravenously. As part of this study, the patient will have blood samples, other tests, exams, and procedures done for study purposes and their standard of care. Patient participation in the study will last for up to 2 years after completion of the last dose of the study drug or until your condition worsens or intolerable adverse events as deemed by the study doctor.
There are possible patient risks to this study that include but are not limited to diarrhea, itching, rash, and a feeling of weakness.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Atezolizumab, Bevacizumab
- Keywords
- EGFR Mutation, Atezolizumab, Bevacizumab, exon L858R, exon 21 L858R
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called TECENTRI
1200 mg IV every 3 weeks
BevacizumabDrug
Also called Avastin
15 mg/kg IV every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| atezolizumab and bevacizumab | Experimental | Atezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks) Receives: Drug: Atezolizumab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Assessed by the Investigator Using RECIST 1.1
Objective response (complete or partial response) rate (ORR) is assessed by the investigator using Response Evaluation Criteria in Solid Tumors RECIST 1.1 (brand name) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 2 years
Secondary outcomes (3)
Progression Free Survival as Measured by RECIST v1.1 RECIST 1.1 (Brand Name) as Assessed by the Investigator.
Progression will be defined as time from start of study therapy to disease progression or death whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median survival time and its 95% CI will be calculated.
Measured: Up to 2 years
Overall Survival as Noted by Follow-up Via Composite of Telephone or Medical Record Review.
Overall survival (OS) is defined as the time from start of study therapy to death from any cause, and patients who are alive at the time of analysis will be censored at the last date of contact.
Measured: Up to 2 years
Number of Participants With AEs as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
All patients who receive at least one dose of study treatment will be included in the safety analysis. The frequencies and percentage of treatment-related adverse events will be tabulated.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2019
- Study start9 Jul 2020
- Primary completion13 Nov 2022
- Study completion15 Jun 2023
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Stinchcombe, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04099836
- Sponsor's protocol ID
- Pro00103723
- Status last verified
- Dec 2023
- First submitted
- 20 Sep 2019
- Last updated
- 26 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share participant level data.
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase 2 Trial of Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib (TOP 1901)
- ClinicalTrials.gov ID
- NCT04099836
- Acronym / sponsor ID
- Pro00103723
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- EGFR Mutation, Atezolizumab, Bevacizumab, exon L858R, exon 21 L858R
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 9 Jul 2020 (actual)
- Primary completion
- 13 Nov 2022 (actual)
- Study completion
- 15 Jun 2023 (actual)
- First posted
- 23 Sep 2019 (actual)
- Results
- Posted 26 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib.
Detailed description
This study will be single arm, open label, phase 2 study which will include patients with stage 4 NSCLC patients with EGFR mutations and who have progressed on osimertinib.
Although both atezolizumab and bevacizumab are approved for the treatment of NSCLC, the combination of atezolizumab and bevacizumab has not been approved by the FDA for the treatment of specific non-small cell lung cancer (NSCLC).
Patients who have one of the following EGRF mutations: exon 19 or exon 21 L858R with progressive disease on osimertinib may be eligible to participate in this study. If enrolled into the study, the study team will give the patient atezolizumab (1200 mg) combined with bevacizumab (15 mg/kg) every 3 weeks intravenously. As part of this study, the patient will have blood samples, other tests, exams, and procedures done for study purposes and their standard of care. Patient participation in the study will last for up to 2 years after completion of the last dose of the study drug or until your condition worsens or intolerable adverse events as deemed by the study doctor.
There are possible patient risks to this study that include but are not limited to diarrhea, itching, rash, and a feeling of weakness.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| atezolizumab and bevacizumab | Experimental | Drug: Atezolizumab, Drug: BevacizumabAtezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Age ≥18 years
- Histologic documentation of primary lung carcinoma, non-squamous histology with EGFR exon deletion 19 or exon 21 L858R mutation
- Stage IV disease according to the 8th Edition of the American Joint Committee on Cancer staging system
- Disease progression on osimertinib
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 (appendix 1)
Key exclusion criteria (19 listed)
- Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component.
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- Other active malignancy ≤ 2 years prior to study cycle 1 day 1 of study therapy. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or adequately treated stage I or II cancer. NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer.
- History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2), unstable angina pectoris, or ventricular arrhythmia with ≤ 6 months
- History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to study cycle 1 day 1 of study therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: TECENTRI1200 mg IV every 3 weeks | Drug | atezolizumab and bevacizumab |
| BevacizumabAlso: Avastin15 mg/kg IV every 3 weeks | Drug | atezolizumab and bevacizumab |
Primary outcome
Objective Response Assessed by the Investigator Using RECIST 1.1
Time frame: Up to 2 years
Objective response (complete or partial response) rate (ORR) is assessed by the investigator using Response Evaluation Criteria in Solid Tumors RECIST 1.1 (brand name) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
3 secondary outcomes
Progression Free Survival as Measured by RECIST v1.1 RECIST 1.1 (Brand Name) as Assessed by the Investigator.
Time frame: Up to 2 years
Overall Survival as Noted by Follow-up Via Composite of Telephone or Medical Record Review.
Time frame: Up to 2 years
Number of Participants With AEs as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. There is no plan to share participant level data.
Related trials for Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Stinchcombe, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Non Small Cell Lung Cancer, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Assessed by the Investigator Using RECIST 1.1 (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2023.