Non-small Cell Lung CancerPhase 1/2NCT02803203
Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers
A Phase 1/2 study testing osimertinib and Bevacizumab in people with Non-small Cell Lung Cancer and EGFR-mutant Lung Cancers, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to test the safety of combining the drugs osimertinib and bevacizumab at different dose levels. The investigators want to find out what effects, good and/or bad, taking osimertinib and bevacizumab has on the patient and lung cancer. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, EGFR-mutant Lung Cancers
- What is being tested?
- osimertinib and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 7 sitesUnited States
- Study dates
- 29 Jun 2016to 1 Mar 2022
- Phase
- Phase 1/2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Advanced biopsy-proven metastatic non-small cell lung cancer
- Somatic activating mutation in EGFR
- No prior treatment with an EGFR TKI
- No prior treatment with a VEGF inhibitor
- Measurable (RECIST 1.1) indicator lesion not previously irradiated
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- Karnofsky performance status (KPS) ≥ 70%
- Age >18 years old
- Adequate organ function
- AST, ALT ≤ 3 x ULN
- Total bilirubin ≤ 1.5x ULN
- Creatinine ≤ 1.5x ULN OR calculated creatinine clearance > 60ml/min
- Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
- Hemoglobin≥8.0 g/dL
- Platelets ≥100,000/mm3
Who cannot join
- Any contra-indications to bevacizumab which include but are not limited to recent
- Any previous venous thromboembolism > NCI CTCAE Grade 3
- Severe uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥ 100mmHg)
- Cardiovascular disease including stroke of myocardial infarction <6 months prior to study enrollment, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrythmia uncontrolled by medication
- Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of steroids) brain metastases are acceptable.
- History of severe proteinuria (urine dipstick ≥ 2+ or 24 hr urine > 2gm/24hr)
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- Prior history of hypertensive crisis or hypertensive encephalopathy
- History of a central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
- Significant vascular disease (e.g. aortic aneurysm requiring surgical repair)≥ 6 months prior to study enrollment
- History of hemoptysis (≥1/2 teaspoon of bright red blood per episode) within the last 3 months
- Evidence of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Current or recent (within 10 days of study drug start) use of aspirin (>325mg daily), clopidogrel (>75mg daily).
- Recent initiation of full dose oral or parental anticoagulants that have not been in place for at least 2 weeks.
- Tumor invading or abutting major blood vessels
- Tumor histology classified by squamous cell histology.
- Any history of abdominal fistula or GI perforation within 6 months of study enrollment
- Pregnant or lactating women
- Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol
- Any radiotherapy within 1 week of starting treatment on protocol
- Any major surgery within 4 weeks of starting treatment on protocol
- Any evidence of clinically significant interstitial lung disease
- Known hypersensitivity to any component of bevacizumab and osimertinib
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memoral Sloan Kettering Basking Ridge
Basking Ridge, New Jersey
Memorial Sloan Kettering commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: A Phase 1/2 Study of Combination Osimertinib and Bevacizumab as Treatment for Patients With EGFR-mutant Lung Cancers
The purpose of this study is to test the safety of combining the drugs osimertinib and bevacizumab at different dose levels. The investigators want to find out what effects, good and/or bad, taking osimertinib and bevacizumab has on the patient and lung cancer. This study will try to find the best dose of osimertinib and bevacizumab given together that does not cause significant side effects. Once the investigators determine that combining osimertinib and bevacizumab is safe, they want to see if the combination is effective in treating lung cancers with the EGFR mutation.
- Being tested
- osimertinib, Bevacizumab
- Keywords
- Osimertinib, bevacizumab, metastatic, 16-033
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
osimertinibDrug
Also called AZD9291
BevacizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| osimertinib and bevacizumab | Experimental | Phase 1:
3+3 dose escalation design 2 dose levels Dose level -1: Osimertinib 40mg daily Maximum accrual = 12 Bevacizumab 15mg/kg q3 weeks Dose level 1: Osimertinib 80mg daily Bevacizumab 15mg/kg q3 Weeks
Phase 2:
Use MTD determined during phase 1 Receives: Drug: osimertinib; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Osimertinib Maximum Tolerated Dose (MTD) (Phase I)
The MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which <1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Measured: 1 year
Bevacizumab Maximum Tolerated Dose (MTD) (Phase I)
The MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which <1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Measured: 1 year
Progression-free Survival (Phase II)
Tumor response will be assessed using RECIST 1.1. A CT chest/abdomen/pelvis will be performed to demonstrate all known areas of measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study start29 Jun 2016
- Primary completion1 Mar 2022
- Study completion1 Mar 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Helena Yu, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02803203
- Sponsor's protocol ID
- 16-033
- Status last verified
- Mar 2022
- First submitted
- 14 Jun 2016
- Last updated
- 22 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Yu HA, Schoenfeld AJ, Makhnin A, Kim R, Rizvi H, Tsui D, Falcon C, Houck-Loomis B, Meng F, Yang JL, Tobi Y, Heller G, Ahn L, Hayes SA, Young RJ, Arcila ME, Berger M, Chaft JE, Ladanyi M, Riely GJ, Kris MG. Effect of Osimertinib and Bevacizumab on Progression-Free Survival for Patients With Metastatic EGFR-Mutant Lung Cancers: A Phase 1/2 Single-Group Open-Label Trial. JAMA Oncol. 2020 Jul 1;6(7):1048-1054. doi: 10.1001/jamaoncol.2020.1260.
PubMed 32463456
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Combination Osimertinib and Bevacizumab as Treatment for Patients With EGFR-mutant Lung Cancers
- ClinicalTrials.gov ID
- NCT02803203
- Acronym / sponsor ID
- 16-033
- Keywords
- Osimertinib, bevacizumab, metastatic, 16-033
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- AstraZeneca, Genentech, Inc.
- Study start
- 29 Jun 2016 (actual)
- Primary completion
- 1 Mar 2022 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 16 Jun 2016 (estimated)
- Results
- Posted 22 Sep 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 test the safety of combining the drugs osimertinib and bevacizumab at different dose levels. The investigators want to find out what effects, good and/or bad, taking osimertinib and bevacizumab has on the patient and lung cancer. This study will try to find the best dose of osimertinib and bevacizumab given together that does not cause significant side effects. Once the investigators determine that combining osimertinib and bevacizumab is safe, they want to see if the combination is effective in treating lung cancers with the EGFR mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| osimertinib and bevacizumab | Experimental | Drug: osimertinib, Drug: BevacizumabPhase 1: 3+3 dose escalation design 2 dose levels Dose level -1: Osimertinib 40mg daily Maximum accrual = 12 Bevacizumab 15mg/kg q3 weeks Dose level 1: Osimertinib 80mg daily Bevacizumab 15mg/kg q3 Weeks Phase 2: Use MTD determined during phase 1 |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent
- Advanced biopsy-proven metastatic non-small cell lung cancer
- Somatic activating mutation in EGFR
- No prior treatment with an EGFR TKI
- No prior treatment with a VEGF inhibitor
Key exclusion criteria (22 listed)
- Any contra-indications to bevacizumab which include but are not limited to recent
- Pregnant or lactating women
- Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol
- Any radiotherapy within 1 week of starting treatment on protocol
- Any major surgery within 4 weeks of starting treatment on protocol
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 |
|---|---|---|
| osimertinibAlso: AZD9291 | Drug | osimertinib and bevacizumab |
| Bevacizumab | Drug | osimertinib and bevacizumab |
Primary outcome
Osimertinib Maximum Tolerated Dose (MTD) (Phase I)
Time frame: 1 year
The MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which <1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Bevacizumab Maximum Tolerated Dose (MTD) (Phase I)
Time frame: 1 year
The MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which <1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Progression-free Survival (Phase II)
Time frame: 12 months
Tumor response will be assessed using RECIST 1.1. A CT chest/abdomen/pelvis will be performed to demonstrate all known areas of measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32463456Yu HA, Schoenfeld AJ, Makhnin A, Kim R, Rizvi H, Tsui D, Falcon C, Houck-Loomis B, Meng F, Yang JL, Tobi Y, Heller G, Ahn L, Hayes SA, Young RJ, Arcila ME, Berger M, Chaft JE, Ladanyi M, Riely GJ, Kris MG. Effect of Osimertinib and Bevacizumab on Progression-Free Survival for Patients With Metastatic EGFR-Mutant Lung Cancers: A Phase 1/2 Single-Group Open-Label Trial. JAMA Oncol. 2020 Jul 1;6(7):1048-1054. doi: 10.1001/jamaoncol.2020.1260.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Helena Yu, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing osimertinib and Bevacizumab in people with Non-small Cell Lung Cancer and EGFR-mutant Lung Cancers, run by Memorial Sloan Kettering Cancer Center at 7 sites 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 15 inclusion and 22 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: finished, as of the sponsor's last update on 22 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 22 Sep 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?
Osimertinib Maximum Tolerated Dose (MTD) (Phase I) (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02803203, which also lists 1 linked publication.
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 22 Sep 2023.