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A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02789345
Recruitment Status : Active, not recruiting
First Posted : June 3, 2016
Last Update Posted : April 22, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The main purpose of this study is to evaluate the safety of ramucirumab or necitumumab in combination with osimertinib in participants with non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Ramucirumab Drug: Necitumumab Drug: Osimertinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase 1 Study With Expansion Cohorts of Ramucirumab or Necitumumab in Combination With Osimertinib in Patients With Advanced T790M-Positive EGFR-Mutant Non-Small Cell Lung Cancer After Progression on First-Line EGFR TKI Therapy
Actual Study Start Date : October 24, 2016
Actual Primary Completion Date : October 19, 2017
Estimated Study Completion Date : May 16, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ramucirumab + Osimertinib

Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle.

Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle.

Drug: Ramucirumab
Administered IV
Other Name: LY3009806

Drug: Osimertinib
Administered orally
Other Name: AZD9291

Experimental: Necitumumab + Osimertinib

Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle.

Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle.

Drug: Necitumumab
Administered IV
Other Name: LY3012211

Drug: Osimertinib
Administered orally
Other Name: AZD9291




Primary Outcome Measures :
  1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Two Cycles (Up to 21 Day Cycles) ]

Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [ Time Frame: Day 1 Cycle 2 to Day 1 Cycle 13 (14 Day Cycles) ]
  2. PK: Cmin of Necitumumab [ Time Frame: Day 1 Cycle 3 to Day 1 Cycle 9 (21 Day Cycles) ]
  3. Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Objective Disease Progression (Approximately 30 Months) ]
  4. Disease Control Rate (DCR): Percentage of Participants with CR, PR or Stable Disease (SD) [ Time Frame: Baseline to Objective Disease Progression (Approximately 30 Months) ]
  5. Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Approximately 30 Months) ]
  6. Progression Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Approximately 30 Months) ]
  7. Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 30 Months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of NSCLC with at least 1 measurable lesion assessable using standard techniques by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
  • Have T790M-positive status using a test validated and performed locally after disease progression on EGFR tyrosine kinase inhibitor (TKI) treatment.
  • Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the time of enrollment.
  • Have serum albumin that is ≥25 grams per liter at the time of enrollment.
  • Have adequate organ function, with all screening labs performed within 7 days of treatment initiation.
  • Have a life expectancy of ≥3 months.
  • Have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Exclusion Criteria:

  • Previous treatment with an EGFR monoclonal antibody (except for past treatment for squamous cell carcinoma of head and neck or metastatic colorectal cancer).
  • Previous treatment with osimertinib or third generation EGFR TKIs.
  • Participants with symptomatic or growing brain metastases less than 4 weeks prior to enrollment.
  • History of drug-induced interstitial lung disease (ILD), ILD, or radiation pneumonitis requiring treatment with steroid prior to study enrollment, or any evidence of clinically active ILD.
  • Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment. Participants with a history of gross hemoptysis (defined as bright red blood of ≥1/2 teaspoon) within 2 months prior to enrollment are excluded.
  • Have experienced any arterial thrombotic event or arterial thromboembolic event, including myocardial infarction, unstable angina (history or evidence of current clinically relevant coronary artery disease of current ≥Class III as defined by Canadian Cardiovascular Society Angina Grading Scale or congestive heart failure of current ≥Class III as defined by the New York Heart Association), cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
  • Have a history of deep vein thrombosis, pulmonary embolism, or any other significant venous thromboembolism (venous catheter thrombosis or superficial venous thrombosis not considered "significant") during the 3 months prior to study enrollment. Participants with venous thromboembolism occurring 3 to 6 months prior to study enrollment are allowed, if being treated with low molecular weight heparin.
  • Have a history of gastrointestinal perforation and/or fistula within 6 months prior to enrollment.
  • Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
  • Have uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating study treatment, despite antihypertensive intervention. CTCAE Version 4.0 defines uncontrolled hypertension as Grade >2 hypertension; clinically, the participant continues to experience elevated blood pressure (systolic >160 millimeters of mercury [mmHg] and/or diastolic >100 mmHg) despite medications.
  • Are receiving chronic therapy with any of the following medications within 7 days prior to enrollment:

    • nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents).
    • other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide).
  • Have radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • Have radiographic evidence of pulmonary intratumor cavitation, regardless of tumor histology.
  • Are receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks prior to enrollment.
  • Have abnormal cardiac findings.
  • Have undergone chest irradiation within 2 weeks prior to study drug administration, have not recovered from all radiation-related toxicities, or requires corticosteroids. A 2-week washout is permitted for focal palliative radiation to non-central nervous system disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02789345


Locations
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United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Villejuif, France, 94805
Korea, Republic of
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Cheong Ju-City, Korea, Republic of, 28644
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Seongnam, Korea, Republic of, 13496
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Seoul, Korea, Republic of, 05505
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Seoul, Korea, Republic of, 06351
Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Madrid, Spain, 28041
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Sevilla, Spain, 41013
Taiwan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tainan, Taiwan, 70403
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Taipei city, Taiwan, 10002
Sponsors and Collaborators
Eli Lilly and Company
AstraZeneca
Investigators
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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
Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02789345    
Other Study ID Numbers: 16357
I4T-MC-JVDL ( Other Identifier: Eli Lilly and Company )
2015-005296-25 ( EudraCT Number )
First Posted: June 3, 2016    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 15, 2020
Keywords provided by Eli Lilly and Company:
T790M
epidermal growth factor receptor (EGFR)
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Ramucirumab
Osimertinib
Necitumumab
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological