Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT02803203

Collaborator

AstraZeneca (Industry), Genentech, Inc. (Industry)

Enrollment

Locations

Arm

Actual Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer EGFR-mutant Lung Cancers	Drug: osimertinib Drug: Bevacizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of Combination Osimertinib and Bevacizumab as Treatment for Patients With EGFR-mutant Lung Cancers

Actual Study Start Date :

Jun 29, 2016

Actual Primary Completion Date :

Mar 1, 2022

Actual Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: osimertinib and bevacizumab 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 Other Names: AZD9291 Drug: Bevacizumab

Arm

Intervention/Treatment

Experimental: osimertinib and bevacizumab

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

Other Names:

AZD9291

Drug: Bevacizumab

Outcome Measures

Primary Outcome Measures

maximum tolerated dose (MTD) (Phase I) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553