Clinical trial NCT01682135: A Study in Participants With Advanced Solid Tumors
Official title: Phase I Study of Ramucirumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-09-10
Enrollment: 28
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: This trial is testing ramucirumab (LY3009806) administered to Chinese participants with advanced solid tumors that are resistant to standard therapy or for whom no standard therapy is available. The purpose of this study is to evaluate how safe ramucirumab is and whether it causes any side effects. The study will also measure how much ramucirumab gets into the blood stream and how long it takes the body to get rid of it.


Eligibility criteria: Inclusion Criteria:

* Chinese participants with histopathologically or cytologically diagnosed advanced solid tumor
* Did not respond to standard therapy or no standard therapy is available
* Measurable or nonmeasurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST)
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 at study entry
* Able to provide written informed consent
* A life expectancy of \>3 months
* Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1500 per cubic millimeter (mm\^3); hemoglobin concentration ≥9 grams per deciliter (g/dL); and platelet count ≥100,000/mm\^3
* Adequate hepatic function, as defined by: Total bilirubin level ≤1.5 x the upper limit of normal (ULN) (in participants with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN with direct bilirubin ≤ 1.5 x ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (or ≤5 x ULN if the participant has liver metastases
* Adequate renal function, as defined by: Serum creatinine level ≤1.5 x ULN; or calculated serum creatinine clearance (Cockcroft-Gault) ≥50 milliliters per minute (mL/min)
* Urinary protein is 0 or 1+ on dipstick but no edema nor serum albumin \< lower level of normal
* Adequate coagulation function, as defined by: International normalized ratio (INR) ≤1.5, or prothrombin time (PT) ≤1.5 x ULN and activated partial thromboplastin time (aPTT) ≤1.5 x ULN (unless receiving anticoagulation therapy)
* Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study treatment

Exclusion Criteria:

* Had chemotherapy or therapeutic radiotherapy within 14 days (6 weeks for nitrosoureas or mitomycin C) before entering the study or the participant has ongoing side effects (≥ Grade 2) due to previously administered agents
* Has obvious evidence of intratumor cavitation
* Has undergone major surgery within 28 days before study entry or has had a central venous access device inserted within 7 days before study entry
* Has a history of gastrointestinal perforation, postoperative bleeding complications, or wound complications from a surgical procedure
* Has elective or planned surgery to be conducted during the trial
* Has documented and/or symptomatic brain or leptomeningeal metastases
* Has uncontrolled ongoing illness, for example: thrombotic or hemorrhagic disorders; hemoptysis; ongoing infection requiring systemic antibiotic treatment; congestive heart failure, angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months; stroke, transient ischemic attack (TIA), or other grade 3-4 arterial thromboembolic event occurring within 6 months; uncontrolled hypertension (≥150/≥90 millimeters of mercury \[mmHg\]); cardiac arrhythmia that requires treatment or asymptomatic sustained ventricular tachycardia; peripheral neuropathy ≥Grade 2; human immunodeficiency virus (HIV) or active, uncontrolled hepatitis, liver cirrhosis at a level of Child-Pugh Class B (or worse), liver cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. (Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis)
* Has a serious or nonhealing wound, ulcer, or bone fracture within 28 days before study entry
* Has experienced any Grade 3 or 4 gastrointestinal bleeding within 3 months before study entry
* Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess \<6 months before randomization, or the participant has a history of poorly controlled or recurrent inflammatory bowel disease (including Crohn's disease or ulcerative colitis)
* Has participated in a clinical study of a non-approved experimental agent or procedure within 4 weeks prior to study entry for small molecules, or 8 weeks before study entry for non-approved monoclonal antibodies
* Has a known allergy to ramucirumab or its excipients, a monoclonal antibody (MAb), or any other therapeutic protein, such as fresh frozen plasma, human serum albumin (HSA), cytokines, or interleukins. If there is suspicion that the participant may have an allergy, the participant should be excluded
* Is pregnant (confirmed by urine or serum pregnancy test) or lactating
* Has known alcohol or drug dependency
* Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs)
* Is not considered to be suitable for this study, in the opinion of the investigator

Primary outcomes:
measure: Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
timeFrame: Baseline through Study Completion (Up to 12 Weeks)
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
timeFrame: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
measure: Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
timeFrame: Cycle 2-5: Predose
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
timeFrame: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
Secondary outcomes:
measure: Duration of Response
timeFrame: Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)
measure: Duration of Stable Disease (SD)
timeFrame: Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)
measure: Time to Disease Progression
timeFrame: Baseline to Progressive Disease (Up to 10 Weeks)
measure: Number of Participants With Anti-Ramucirumab Antibodies
timeFrame: Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion
measure: Number of Participants With Best Objective Response (BOR)
timeFrame: Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: 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.
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:
citation: Cao J, Ji D, Chen Z, Shen W, Wang J, Li B, Chi H, Long A, Gao L, Li J. Phase I Dose-Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors. Oncologist. 2017 Jun;22(6):638-e56. doi: 10.1634/theoncologist.2017-0137. Epub 2017 May 2.