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

NCT01005355 | Completed Phase 1 Results DMC

• 3 other identifiers: 13898CP12-0816I4T-IE-JVBI
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Keywords

Solid tumor; recombinant human IgG1; MAB; monoclonal antibody; VEGFR 2; human vascular endothelial growth factor receptor 2

Outcome Measures

Primary Outcomes (17)

• 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

• 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

• 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

• 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 \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).

  Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).

  Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (1)

• Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)

  Baseline to study completion up to 48 weeks

Study Arms (1)

IMC-1121B

EXPERIMENTAL

Participants receiving IMC-1121B intravenously

Biological: IMC-1121B

Interventions

IMC-1121B BIOLOGICAL

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.

Also known as: RAMUCIRUMAB, LY3009806

IMC-1121B

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Parexel: collaborator

Study Sites (1)

ImClone Investigational Site

Tokyo, 104-0045, Japan

Location

Related Publications (1)

• 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.

  PMID: 28158463 DERIVED

MeSH Terms

Interventions

Ramucirumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2009
• First Posted: October 30, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: June 18, 2014
• Results First Posted: June 18, 2014

Record last verified: 2014-05

Locations

JP (1)