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Non Small Cell Lung CancerPhase 2NCT03909334

Study of Osimertinib With and Without Ramucirumab in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

A Phase 2 study testing Osimertinib and Ramucirumab in people with Non Small Cell Lung Cancer and EGFR Gene Mutation, run by Xiuning Le at 12 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The primary objective of the study is to evaluate the efficacy of osimertinib plus ramucirumab versus osimertinib alone using progression free survival (PFS). Events associated with PFS include: disease progression per RECIST 1.1 and death due to any cause. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Osimertinib and Ramucirumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
12 sitesUnited States
Study dates
25 Jul 2019to Jan 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • Histologically or cytologically confirmed non-squamous, non-small cell lung cancer.
  • Locally advanced or metastatic disease, not amenable to curative surgery or radiotherapy.
  • Patients must have one of the following:
  • NSCLC which harbours EGFR Exon 19 deletion.
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  • NSCLC which harbours EGFR L858R mutation. EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test (either from tissue or ctDNA from blood is allowed). If EGFR deletion/mutation testing has not been done, it should be ordered per standard of care.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A).
  • Measurable disease per RECIST 1.1.
  • Patients with brain metastases are eligible if they are asymptomatic, are treated, or are neurologically stable for at least two weeks without the use of steroids or on stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent). These criteria must be met on day of consent.
  • Ability to take pills by mouth.
  • Previous treatment with cytotoxic chemotherapy or immunotherapy is allowed.
  • Patients must have adequate hematologic, coagulation, hepatic, and renal function. All laboratory tests must be obtained less than 4 weeks from study entry. This includes:
  • ANC >/= 1,500/mm3
  • platelet count >/=100,000/mm3
  • HgB ≥ 9 g/dL (may be with transfusion)
  • Creatinine ≤ 1.5x ULN or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
  • The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol).
  • Total Serum Bilirubin ≤ 1.5 x ULN (Patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
  • SGOT, SGPT ≤ 3 X ULN if no liver metastasis present
  • SGOT, SGPT ≤ 5 X ULN if liver metastasis present
  • The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x upper limits of normal [ULN]. Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤ 3.0. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices.
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days of starting of treatment. See the protocol for additional details.
  • Females of childbearing potential and Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use adequate contraception as outlined in the protocol.

Who cannot join

  • Subjects unable to stop use of medications that are potent inducers of CYP3A4 or known to prolong QT interval. See Appendix B for additional details.
  • Any prior history of other cancer within the prior 2 years with the exception of: adequately treated basal cell carcinoma, cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ, melanoma in situ or ductal carcinoma in situ [DCIS], localized Gleason 6 prostate cancer, papillary thyroid cancer or other non-melanoma skin cancers.
  • Previous treatment with any EGFR TKIs, including erlotinib, gefitinib, afatinib, avitinib, dacomitinib, rociletinib, or osimertinib.
  • Previous treatment with any anti-VEGF medications, including vandetinib, nintedanib, bevacizumab, or ramucirumab.
  • Spinal cord compression unless asymptomatic or stable for at least 2 weeks prior to start of study treatment.
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
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  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Patients with uncharacterized eye disorders.
  • History of hypersensitivity of osimertinib or ramucirumab (or active or inactive excipients of osimertinib or ramucirumab).
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec.
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250msec.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
  • The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
  • The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
  • The patient has experienced any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy.
  • The patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy.
  • The patient has cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
  • Any hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
  • The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
  • The patient has undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Summit Medical Group, PA

    Berkeley Heights, New Jersey, 07922

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana Univesity Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • New York University Cancer Center

    New York, New York, 10016

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Georgetown University

    Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

Official title: An Open-Label Randomized Phase II Study of Combining Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor (TKI)-naïve Epidermal Growth Factor Receptor (EGFR)-Mutant Locally Advanced or Metastatic NSCLC

The primary objective of the study is to evaluate the efficacy of osimertinib plus ramucirumab versus osimertinib alone using progression free survival (PFS). Events associated with PFS include: disease progression per RECIST 1.1 and death due to any cause. A total of 150 patients will be enrolled and randomized in a 2:1 fashion (osimertinib plus ramucirumab vs. osimertinib) to the two treatment arms according to the following stratification factors: types of epidermal growth factor receptor (EGFR) mutations and presence of brain metastasis.

Being tested
Osimertinib, Ramucirumab
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 Tagrisso

    Osimertinib 80 mg orally on Day 1

  • RamucirumabDrug

    Also called Cyramza

    Ramucirumab 10 mg/kg intravenously (IV) over 60 minutes for first infusion and if tolerated subsequent infusions may be over 30 minutes

Study groups in NCT03909334
Study groupRoleWhat they receive
Arm A (Osimertinib and Ramucirumab)Active comparatorOsimertinib and Ramucirumab
Receives: Drug: Osimertinib; Drug: Ramucirumab
Arm B (Osimertinib)Active comparatorOsimertinib
Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    Progression free survival (PFS) time will be calculated from the date of randomization to disease progression or death from any cause, whichever occurs the first.

    Measured: 3 years

Secondary outcomes (4)

  1. Objective Response Rate (ORR)

    Objective Response Rate (ORR) is defined as the number (%) of subjects with measurable disease with at least one visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of ORR.

    Measured: 1 year

  2. Disease control rate (DCR)

    Disease control rate (DCR) is defined as the percentage of subjects who have a best overall response of CR or PR or stable disease (SD).

    Measured: 2 years

  3. Overall survival (OS)

    Overall survival (OS) time is defined from the date of randomization to death date. A patient is censored at the last follow-up date if death has not been observed.

    Measured: 3 years

  4. Assess frequency and severity of adverse events

    Toxicities will be measured in frequency and severity using CTCAE v5

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2019
  2. Study start25 Jul 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03909334
Sponsor's protocol ID
HCRN LUN18-335
Status last verified
Apr 2026
First submitted
8 Apr 2019
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Le X, Patel JD, Shum E, Baik C, Sanborn RE, Shu CA, Kim C, Fidler MJ, Hall R, Elamin YY, Tu J, Blumenschein G, Zhang J, Gibbons D, Gay C, Mohindra NA, Chae Y, Boumber Y, Sabari J, Santana-Davila R, Rogosin S, Herzberg B, Creelan B, Pellini B, Tanvetyanon T, Heeke S, Hernandez M, Gray JE, Saltos A, Heymach JV. A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor-Naive EGFR-Mutant Metastatic Non-Small Cell Lung Cancer (RAMOSE trial). J Clin Oncol. 2025 Feb;43(4):403-411. doi: 10.1200/JCO.24.00533. Epub 2024 Oct 8.

    PubMed 39378386

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib and Ramucirumab in people with Non Small Cell Lung Cancer and EGFR Gene Mutation, run by Xiuning Le at 12 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 24 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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?

Progression Free Survival (PFS) (time frame: 3 years). 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 NCT03909334, 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 17 Apr 2026.

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