Clinical trial NCT01005355: Study of IMC-1121B in Patients With Advanced Solid Tumors
Official title: Phase 1 Study of IMC-1121B in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Solid tumor
recombinant human IgG1
MAB
monoclonal antibody
VEGFR 2
human vascular endothelial growth factor receptor 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2009-10-30
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is testing the investigational drug IMC-1121B administered to Japanese participants with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available. The rationale for performing this trial is to establish the safety profile and the pharmacokinetics of IMC-1121B.

Detailed description: This single center, open-label, single-arm, Phase 1 study will enroll approximately 15 to 18 participants. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Participants will receive IMC-1121B, administered intravenously, once every 2 or 3 weeks for 6 weeks (one cycle). After one cycle of treatment, participants who have an objective response or stable disease may continue to receive IMC-1121B at the same dose and schedule until disease progression or other withdrawal criteria are met. A minimum of three participants will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all participants complete one cycle of therapy.

Participants will be enrolled sequentially into each cohort.

A completed participant will be either a participant who completes the initial 6 week treatment period (Cycle 1) or a participant who discontinues therapy for an IMC-1121B related toxicity during Cycle 1. Participants who do not complete the first 6 weeks of treatment for reasons other than an IMC-1121B -related toxicity will be replaced. Toxicity data for each cohort will be reviewed prior to dose escalation. Upon completion of all required safety evaluations during the initial 6 weeks, the next cohort of new participants will be treated at the next higher dose level using a dose escalation scheme.

Eligibility criteria: Inclusion Criteria:

* Solid tumor participant who was been histopathologically or cytologically documented.
* Advanced primary or recurrent solid tumors participant who has not responded to standard therapy or no standard therapy is available.
* The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST).
* The participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 at study entry.
* The participant is able to provide written informed consent.
* The participant is age 20 years or older.
* The participant has a life expectancy of \> 3 months.
* The participant has adequate hematologic function, as defined by:
* An absolute neutrophil count (ANC) \> 1500/cubic millimeter (mm³) or /microliter (µL)
* A hemoglobin level \> 10 grams/deciliter (g/dL)
* A platelet count \> 100,000/mm³ or /µL
* The participant has adequate hepatic function, as defined by:
* A total bilirubin level \< 1.8 milligrams/deciliter (mg/dL)
* Aspartate transaminase (AST) levels \< 86 International Units/liter (IU/L)
* Alanine transaminase (ALT) levels ≤ 86 IU/L
* The participant has adequate renal function, as defined by:
* Serum creatinine level ≤ 1.5 mg/dL, or
* Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 milliliters/minute (mL/min)
* The participant's urinary protein is 0 on dipstick or 1+ but participant does not have edema nor serum albumin \< lower level of normal (LLN).
* The participant has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5.
* The participant agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study treatment.

Exclusion Criteria:

* The participant has had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or participant has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier.
* The participant has obvious evidence of intratumor cavitation.
* The participant has undergone major surgery (example, laparotomy, thoracotomy, removal of organ\[s\]) within 28 days prior to study entry, or subcutaneous venous access device placement within 7 days prior to study entry.
* The participant has a history of postoperative bleeding complications or wound complications from a surgical procedure.
* The participant has elective or planned surgery to be conducted during the trial.
* The participant has documented and/or symptomatic brain or leptomeningeal metastases. (Participants who are clinically stable \[no symptoms during 4 weeks prior to the enrollment\] with an assessment that no further treatment \[radiation, surgical excision, and administration of steroids\] is required, are permitted to enter the study.)
* The participant has uncontrolled intercurrent illness including, but not limited to:
* Thrombotic or hemorrhagic disorders
* Hemoptysis (approximately one-half of a teaspoon)
* Ongoing or active infection requiring systemic antibiotic treatment
* Congestive heart failure (Class III or IV of the New York Heart Association classification for heart disease)
* Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
* Uncontrolled hypertension (systolic blood pressure \> 150 millimeters of mercury (mmHg), diastolic blood pressure \> 95 mm Hg)
* Cardiac arrhythmia requires treatment \[National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), Grade 3\], or asymptomatic sustained ventricular tachycardia)
* Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE v 3.0)
* The participant has participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies.
* The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating.

Primary outcomes:
measure: Number of Participants With Drug-Related Adverse Events
timeFrame: Baseline to study completion up to 48 weeks
measure: IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2
timeFrame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2
timeFrame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
timeFrame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2
timeFrame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2
timeFrame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2
timeFrame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
timeFrame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
measure: IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2
timeFrame: Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle
measure: IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5
timeFrame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose
Secondary outcomes:
measure: Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)
timeFrame: Baseline to study completion up to 48 weeks
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: ImClone Investigational Site
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: Nokihara H, Yamamoto N, Yamada Y, Honda K, Asahina H, Tamura Y, Hozak RR, Gao L, Suzukawa K, Enatsu S, Tamura T. A phase 1 study of ramucirumab in Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2017 Apr 1;47(4):298-305. doi: 10.1093/jjco/hyx008.