Advanced Solid Tumor
Conditions
Keywords
Safety
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.
Interventions
DRUGRamucirumab
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab | 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: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days. |
| PK: Maximum Concentration (Cmax) of Ramucirumab | 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: Cmax of Ramucirumab was evaluated. |
| PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose | Ctrough of Ramucirumab was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Anti-Ramucirumab Antibodies | C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose | 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). |
| Number of Participants With Injection Site Reactions (ISRs) | 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) | 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. |
Countries
Japan, United States
Participant flow
Pre-assignment details
Completers included participants who had progressive disease, off protocol therapy due to toxicity and having completed the short-term follow-up, death due to any cause.
Participants by arm
| Arm | Count |
|---|---|
| Ramucirumab Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Study Terminated by Sponsor | 1 |
Baseline characteristics
| Characteristic | Ramucirumab |
|---|---|
| Age, Continuous | 66.67 years STANDARD_DEVIATION 5.508 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab
PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days.
Time frame: 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
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Ramucirumab | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab | NA nanograms*hours/milliliter (ng*hr/mL) |
Primary
PK: Maximum Concentration (Cmax) of Ramucirumab
PK: Cmax of Ramucirumab was evaluated.
Time frame: 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
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Ramucirumab | PK: Maximum Concentration (Cmax) of Ramucirumab | NA nanograms per milliliter (ng/mL) |
Primary
PK: Serum Trough Concentration (Ctrough) of Ramucirumab
Ctrough of Ramucirumab was evaluated.
Time frame: C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ramucirumab | PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C1D8 | 12.6 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 79 |
| Ramucirumab | PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C1D15 | 20.9 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 41.6 |
| Ramucirumab | PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C2D1 | NA microgram per milliliter (µg/mL) | — |
| Ramucirumab | PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C2D8 | NA microgram per milliliter (µg/mL) | — |
| Ramucirumab | PK: Serum Trough Concentration (Ctrough) of Ramucirumab | C3D1 | NA microgram per milliliter (µg/mL) | — |
Secondary
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.
Time frame: 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)
Population: All randomized participants who received at least one dose of study drug and had at least one post dose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab | Number of Participants With Injection Site Reactions (ISRs) | 1 participants |
Secondary
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).
Time frame: C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose
Population: Zero participants were analyzed. Data not collected.