A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Participants With EGFR Mutation-Positive Metastatic NSCLC

ID: NCT02411448
Status: Recruiting
Phase: Phase 3
Start Date: May 01, 2015
First Submitted: April 03, 2015
Last Updated: February 23, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company
Location: Canada, France, Germany, Greece, Hong Kong, Italy, Japan, Korea, Republic of, Romania, Spain, Taiwan, Turkey, United Kingdom, United States
Conditions: Metastatic Non-Small Cell Lung Cancer
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Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in participants with stage IV non small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).

Detailed Description

Condition or disease Intervention/treatment Phase

Metastatic Non-Small Cell Lung Cancer

Drug: Ramucirumab
Other Names
LY3009806
Drug: Placebo
Other Names
Drug: Erlotinib
Other Names
Phase 3

Tracking Information

First Submitted DateApril 03, 2015
Last Update Posted DateFebruary 23, 2018
Start DateMay 01, 2015
Anticipated Completion DateAugust 01, 2021
Primary Completion DateOctober 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Progression Free Survival (PFS) [Time Frame: Randomization to Measured Progressive Disease or Death from Any Cause (Estimated as 33 Months)]

  • Number of Participants with One or More Drug Related Adverse Events (AEs) or Any Serious AEs [Time Frame: Cycle 1 Day 1 through End of Study (Estimated as 34 Months)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Overall Survival (OS) [Time Frame: Randomization to Date of Death from Any Cause (Estimated as 47 Months)]

  • Objective Response Rate (ORR) [Time Frame: Randomization to Disease Progression (Estimated as 33 Months)]

  • Disease Control Rate (DCR) [Time Frame: Randomization to Disease Progression (Estimated as 33 Months)]

  • Duration of Response (DoR) [Time Frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated as 33 Months)]

  • Pharmacokinetics (PK): Minimum Concentration (CMIN) of Ramucirumab [Time Frame: Cycle 2 Predose through Cycle 14 Predose (Estimated as 28 Months)]

  • Number of Participants with Anti-Ramucirumab Antibodies [Time Frame: Cycle 1 Predose through Follow-up (Estimated as 34 Months)]

  • Change from Baseline on the Lung Cancer Symptom Scale (LCSS) [Time Frame: Baseline, End of Study (Estimated as 33 Months)]

  • Change from Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) [Time Frame: Baseline, End of Study (Estimated as 33 Months)]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Participants With EGFR Mutation-Positive Metastatic NSCLC
Official TitleA Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer
Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in participants with stage IV non small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).

Detailed Description

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
462
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Metastatic Non-Small Cell Lung Cancer
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Ramucirumab

Administered IV

Other Names
LY3009806
Drug: Placebo

Administered IV

Other Names
Drug: Erlotinib

Administered orally

Other Names
Study Groups/Cohorts
Ramucirumab + Erlotinib
(Part A) 10 milligrams per kilogram (mg/kg) ramucirumab every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. (Part B) 10 mg/kg ramucirumab every 2 weeks IV in combination with 150 mg erlotinib daily orally . Participants may continue to receive treatment until discontinuation criteria are met.

Placebo + Erlotinib
(Part A) Not Applicable (Part B) Placebo every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Study Arms
Placebo Comparator Placebo + Erlotinib
(Part A) Not Applicable (Part B) Placebo every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Placebo
Administered IV

Placebo Comparator Placebo + Erlotinib
(Part A) Not Applicable (Part B) Placebo every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Erlotinib
Administered orally

Experimental Ramucirumab + Erlotinib
(Part A) 10 milligrams per kilogram (mg/kg) ramucirumab every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. (Part B) 10 mg/kg ramucirumab every 2 weeks IV in combination with 150 mg erlotinib daily orally . Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Ramucirumab
Administered IV

Experimental Ramucirumab + Erlotinib
(Part A) 10 milligrams per kilogram (mg/kg) ramucirumab every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. (Part B) 10 mg/kg ramucirumab every 2 weeks IV in combination with 150 mg erlotinib daily orally . Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Erlotinib
Administered orally

Arm Intervention/Treatment
Placebo Comparator Placebo + Erlotinib
(Part A) Not Applicable (Part B) Placebo every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Placebo
Placebo Comparator Placebo + Erlotinib
(Part A) Not Applicable (Part B) Placebo every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Erlotinib
Experimental Ramucirumab + Erlotinib
(Part A) 10 milligrams per kilogram (mg/kg) ramucirumab every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. (Part B) 10 mg/kg ramucirumab every 2 weeks IV in combination with 150 mg erlotinib daily orally . Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Ramucirumab
Experimental Ramucirumab + Erlotinib
(Part A) 10 milligrams per kilogram (mg/kg) ramucirumab every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. (Part B) 10 mg/kg ramucirumab every 2 weeks IV in combination with 150 mg erlotinib daily orally . Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Erlotinib

Recruitment Information

Recruitment Status:Recruiting
Enrollment462
Completion DateAugust 01, 2021
Eligibility Criteria: Inclusion Criteria:
- Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009).
- Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation (Example 19 del and L858R).
- Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable.
- At least one measurable lesion.
- Life expectancy of at least 3 months.

Exclusion Criteria:
- Known T790M EGFR mutation.
- Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases.
- Serious illness or medical condition.
- Ongoing treatment with CYP3A4 inducers or strong inhibitors.
- Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.
- History of gross hemoptysis.
- Significant bleeding disorders.
- Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
- Radiographic evidence of intratumor cavitation.
- History of gastrointestinal perforation within last 6 months.
- History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection.
- History of any arterial thrombotic event within 6 months prior to enrollment.
- The participant has any known significant ophthalmologic abnormalities of the surface of the eye.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Canada
France
Germany
Greece
Hong Kong
Italy
Japan
Korea, Republic of
Romania
Spain
Taiwan
Turkey
United Kingdom
United States

Administrative Information

NCT Number:NCT02411448
Other Study ID Numbers
15540
I4T-MC-JVCY
2014-004824-22
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
Not Available
Investigators
Study Director
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company