Clinical trial NCT02803203: Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers
Official title: A Phase 1/2 Study of Combination Osimertinib and Bevacizumab as Treatment for Patients With EGFR-mutant Lung Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
EGFR-mutant Lung Cancers
Keywords: Osimertinib
bevacizumab
metastatic
16-033
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Genentech, Inc.
First posted: 2016-06-16
Enrollment: 49
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* Any contra-indications to bevacizumab which include but are not limited to recent

  1. Any previous venous thromboembolism \> NCI CTCAE Grade 3
  2. Severe uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥ 100mmHg)
  3. 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
  4. Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of steroids) brain metastases are acceptable.
  5. History of severe proteinuria (urine dipstick ≥ 2+ or 24 hr urine \> 2gm/24hr)
  6. Prior history of hypertensive crisis or hypertensive encephalopathy
  7. History of a central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
  8. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair)≥ 6 months prior to study enrollment
  9. History of hemoptysis (≥1/2 teaspoon of bright red blood per episode) within the last 3 months
  10. Evidence of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  11. Current or recent (within 10 days of study drug start) use of aspirin (\>325mg daily), clopidogrel (\>75mg daily).
  12. Recent initiation of full dose oral or parental anticoagulants that have not been in place for at least 2 weeks.
  13. Tumor invading or abutting major blood vessels
  14. Tumor histology classified by squamous cell histology.
  15. 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

Primary outcomes:
measure: Osimertinib Maximum Tolerated Dose (MTD) (Phase I)
timeFrame: 1 year
measure: Bevacizumab Maximum Tolerated Dose (MTD) (Phase I)
timeFrame: 1 year
measure: Progression-free Survival (Phase II)
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memoral Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Helena Yu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.