A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer

A Phase 1, Nonrandomized, Open-Label Investigation of Subcutaneous Ramucirumab Administration in Participants With Advanced Solid Tumors

The purpose of this study in participants with advanced cancer is to learn more about the safety of ramucirumab when given by injection under the skin (subcutaneous injection). The study will also measure how much ramucirumab gets into the bloodstream and how long it takes the body to get rid of it.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Ramucirumab

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Osaka Sayama-shi, Osaka, Japan, 589 8511
      • Kindai University Hospital
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute- Carolinas Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

• In the judgment of the investigator, be an appropriate candidate for experimental therapy and:

  • For Cohort A only: Have exhausted all anticancer treatments with proven clinical benefit OR

  • For Cohorts B and C only: Must have one of the three conditions below:

    • Have exhausted all anti-cancer treatments with proven clinical benefit, OR
    • Have hepatocellular carcinoma or gastric cancer who have received prior treatment, and where IV ramucirumab monotherapy is clinically acceptable treatment after progression OR
    • Have a diagnosis for which IV ramucirumab in combination with additional anticancer therapy is clinically acceptable treatment
    • Additionally, it must be clinically acceptable to delay initiation of the combination partner for 3 weeks from the initiation of ramucirumab dosing.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• Have discontinued all previous treatments for cancer with adequate wash-out period and recovered from the acute effects of therapy.
• Have adequate hematologic, hepatic, and renal functions and electrolytes.
• Males and females of child-bearing potential must agree to use highly effective contraceptive methods during study treatment and for at least 84 days/12 weeks following the last dose of study drug.

Exclusion Criteria:

• Have uncontrolled hypertension defined as systolic blood pressure (BP) >150 mmHg or diastolic BP >90 mmHg despite standard medical management.
• Have significant bleeding disorders or experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
• Have hepatic impairment (such as severe liver cirrhosis Child-Pugh B [or worse], cirrhosis with a history of hepatic encephalopathy, clinically meaningful ascites requiring ongoing treatment with diuretics and/or paracentesis, or history of hepatorenal syndrome).
• Have experienced any arterial thromboembolic events (ATEs), including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, ≤6 months prior to randomization.
• The participant has clinically relevant congestive heart failure (CHF; New York Heart Association [NYHA] Grade ≥2) or symptomatic or poorly controlled cardiac arrhythmia.
• Have symptomatic central nervous system (CNS) metastases. Screening is not required.
• Have history of GI perforation and/or fistula within 6 months prior to enrollment.
• Have an active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness.
• Have a serious or non-healing wound, ulcer, or bone fracture within 4 weeks prior to enrollment.
• Have received IV ramucirumab in the past.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramucirumab; Participants received starting dose of 700 milligram (mg) ramucirumab loading dose (LD) subcutaneously (SC) followed, a week later, by 350 mg ramucirumab maintenance dose (MD) administered SC once a week.	Drug: Ramucirumab; Administered SC; Other Names: LY3009806

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab	PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days.	Cycle (C) 1 Day (D) 1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose
PK: Maximum Concentration (Cmax) of Ramucirumab	PK: Cmax of Ramucirumab was evaluated.	C1D1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose
PK: Serum Trough Concentration (Ctrough) of Ramucirumab	Ctrough of Ramucirumab was evaluated.	C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Anti-Ramucirumab Antibodies	Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).	C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose
Number of Participants With Injection Site Reactions (ISRs)	The number of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	Cycle 1, Cycle 2, Cycle 3: D1, D8, D15, D22: 5-15 min, 60 min post injection; C1D2: 24 hours (h) post injection; C1D4 (± 1 day)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): May 25, 2021

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Safety
• Additional Relevant MeSH Terms: Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: 17800; I4T-MC-JVDU (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No