Clinical trial NCT04557384: A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer
Official title: A Phase 1, Nonrandomized, Open-Label Investigation of Subcutaneous Ramucirumab Administration in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Safety
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab
timeFrame: 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
measure: PK: Maximum Concentration (Cmax) of Ramucirumab
timeFrame: 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
measure: PK: Serum Trough Concentration (Ctrough) of Ramucirumab
timeFrame: C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose
Secondary outcomes:
measure: Percentage of Participants With Anti-Ramucirumab Antibodies
timeFrame: C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose
measure: Number of Participants With Injection Site Reactions (ISRs)
timeFrame: 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)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Omaha
country: United States
facility: Oncology Hematology West
state: Nebraska
city: Charlotte
country: United States
facility: Levine Cancer Institute- Carolinas Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Osaka Sayama-shi
country: Japan
facility: Kindai University Hospital
state: Osaka
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: