Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

NCT02803203 | Completed Phase 1 Results

• 1 other identifier: 16-033
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

Osimertinib; bevacizumab; metastatic; 16-033

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  12 months

Study Arms (1)

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

Drug: osimertinib; Drug: Bevacizumab

Interventions

osimertinib DRUG

Also known as: AZD9291

osimertinib and bevacizumab

Bevacizumab DRUG

osimertinib and bevacizumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator
• Genentech, Inc.: collaborator

Study Sites (7)

Memoral Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• 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.

  PMID: 32463456 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

osimertinib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Helena Yu, MD
• Organization: Memorial Sloan Kettering Cancer Center

YuH@mskcc.org

646-608-3912

Study Officials

• Helena Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: June 16, 2016
• Study Start: June 29, 2016
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: September 22, 2023
• Results First Posted: September 22, 2023

Record last verified: 2022-03

Locations

US (7)