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Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

Primary Purpose

Non-small Cell Lung Cancer, EGFR-mutant Lung Cancers

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
osimertinib
Bevacizumab
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Osimertinib, bevacizumab, metastatic, 16-033

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memoral Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

osimertinib and bevacizumab

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
June 14, 2016
Last Updated
August 29, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
AstraZeneca, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02803203
Brief Title
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 29, 2016 (Actual)
Primary Completion Date
March 1, 2022 (Actual)
Study Completion Date
March 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
AstraZeneca, Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, EGFR-mutant Lung Cancers
Keywords
Osimertinib, bevacizumab, metastatic, 16-033

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
osimertinib and bevacizumab
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
osimertinib
Other Intervention Name(s)
AZD9291
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Primary Outcome Measure Information:
Title
Osimertinib Maximum Tolerated Dose (MTD) (Phase I)
Description
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.
Time Frame
1 year
Title
Bevacizumab Maximum Tolerated Dose (MTD) (Phase I)
Description
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.
Time Frame
1 year
Title
Progression-free Survival (Phase II)
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
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 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memoral Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32463456
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.
Results Reference
derived
Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

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Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

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