Study of IMC-1121B in Patients With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

Phase 1 Study of IMC-1121B in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005355
• Other study ID #: 13898
• Secondary ID: CP12-0816I4T-IE-
• Status: Completed
• Phase: Phase 1
• First received: October 5, 2009
• Last updated: May 16, 2014
• Start date: September 2009
• Est. completion date: February 2011

Study information

• Verified date: May 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• IMC-1121B
Cycle 1: Upon completion of enrollment criteria confirmed at screening, the first dose of study medication should be administered within 7 days. The infusion will be planned every 2 weeks or every 3 weeks on the same day of the week of the first infusion. Dose escalation to Cohort 2 may occur in the absence of a dose-limiting toxicity (DLT) in the first three participants treated in Cohort 1 during the initial 6-week dosing period (Cycle 1). The same procedure will be followed for dose escalation from Cohort 2 to Cohort 3. If 1 of 3 participants in any cohort experiences a DLT in the first 6 weeks (Cycle 1), 3 additional participants will be enrolled in that cohort. Dose escalation to the next cohort may occur if less that 2 of 6 participants experience a DLT during Cycle 1.

Locations

Country	Name	City	State
Japan	ImClone Investigational Site	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Parexel

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Drug-Related Adverse Events	Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade =3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.	Baseline to study completion up to 48 weeks	Yes
Primary	IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2		Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2	AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-8)] and for Cycle 2 is AUC over a dosing interval (AUCt).	Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2		Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2		Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2		Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2	AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-8)] and for Cycle 2 is AUC over a dosing interval (AUCt).	Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2		Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose	No
Primary	IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2		Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle	No
Primary	IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5	Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.	Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose	No
Secondary	Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)	Data presented are the number of participants with treatment emergent antibody positive.	Baseline to study completion up to 48 weeks	No