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

NCT03909334 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN LUN18-335
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 12

Brief 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. 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.

Conditions

Non Small Cell Lung Cancer; EGFR Gene Mutation; Advanced Cancer; Metastatic Cancer

Outcome Measures

Primary Outcomes (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.

  3 years

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  1 year

• Disease control rate (DCR)

  2 years

• Overall survival (OS)

  3 years

• Assess frequency and severity of adverse events

  2 years

Study Arms (2)

Arm A (Osimertinib and Ramucirumab)

ACTIVE COMPARATOR

Osimertinib and Ramucirumab

Drug: Osimertinib; Drug: Ramucirumab

Arm B (Osimertinib)

ACTIVE COMPARATOR

Osimertinib

Drug: Osimertinib

Interventions

Osimertinib DRUG

Osimertinib 80 mg orally on Day 1

Also known as: Tagrisso

Arm A (Osimertinib and Ramucirumab); Arm B (Osimertinib)

Ramucirumab DRUG

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

Also known as: Cyramza

Arm A (Osimertinib and Ramucirumab)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Xiuning Le: lead
• M.D. Anderson Cancer Center: collaborator
• Eli Lilly and Company: collaborator

Study Sites (12)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Univesity Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Summit Medical Group, PA

Berkeley Heights, New Jersey, 07922, United States

Location

New York University Cancer Center

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 39378386 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

osimertinib; Ramucirumab

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

Study Officials

• Xiuning Le, MD PhD

  MD Anderson

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 10, 2019
• Study Start: July 25, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)