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

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
ImClone LLC
ClinicalTrials.gov Identifier:
NCT01005355
First received: October 5, 2009
Last updated: September 12, 2011
Last verified: September 2011
History of Changes
  Purpose

This trial is testing the investigational drug IMC-1121B administered to Japanese patients 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.


Condition Intervention Phase
Advanced Solid Tumors
 Biological: IMC 1121B
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of IMC-1121B in Patients With Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]
  • IMC-1121B Pharmacokinetics - Maximum plasma concentration (Cmax) - Cohorts 1 & 2 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, and 15, of Weeks 1, 2, 3, 7, 8, and 9 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Maximum plasma concentration (Cmax) - Cohorts 1 & 2 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohorts 1 & 2 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, and 15, of Weeks 1, 2, 3, 7,8, and 9 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohorts 1 & 2 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Half-Life (t 1/2) - Cohorts 1 & 2 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, and 15, of Weeks 1, 2, 3, 7,8, and 9 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Half-Life (t 1/2) - Cohorts 1 & 2 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Steady State Volume of Distribution (Vss) - Cohorts 1 & 2 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, and 15, of Weeks 1, 2, 3, 7,8, and 9 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Steady State Volume of Distribution (Vss) - Cohorts 1 & 2 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Maximum plasma concentration (Cmax) - Cohort 3 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, 15, and 22 of Weeks 1, 2, 3, 4, 7, 8, 9, and 10 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Maximum plasma concentration (Cmax) - Cohort 3 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, 15, and 22 of Weeks 1, 2, 3, 4, 7, 8, 9, and 10 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Half-Life (t 1/2) - Cohort 3 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, 15, and 22 of Weeks 1, 2, 3, 4, 7, 8, 9, and 10 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Half-Life (t 1/2) - Cohort 3 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Steady State Volume of Distribution (Vss) - Cohort 3 [ Time Frame: Cycles 1 & 2: Baseline, Days 1, 2, 3, 5, 8, 12, 15, and 22 of Weeks 1, 2, 3, 4, 7, 8, 9, and 10 ] [ Designated as safety issue: No ]
  • IMC-1121B Pharmacokinetics - Steady State Volume of Distribution (Vss) - Cohort 3 [ Time Frame: Cycles 3, 4, & 5: Day 1 of Weeks 13, 19, and 25 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Screen for the development of circulating antibodies against IMC-1121B (immunogenicity). [ Time Frame: 10 months ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: September 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC 1121B
Patients receiving IMC 1121B intravenously
 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 DLT in the first three pts 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 pts in any cohort experiences a DLT in the first 6 weeks (Cycle 1), 3 additional pts will be enrolled in that cohort. Dose escalation to the next cohort may occur if less that 2 of 6 pts experience a DLT during Cycle 1.
Other Name: RAMUCIRUMAB

Detailed Description:

This single center, open-label, single-arm, Phase 1 study will enroll approximately 15 to 18 patients. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Patients will receive IMC-1121B, administered intravenously, once every 2 or 3 weeks for 6 weeks (one cycle). After one cycle of treatment, patients 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 patients will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all patients complete one cycle of therapy.

Patients will be enrolled sequentially into each cohort.

A completed patient will be either a patient who completes the initial 6 week treatment period (Cycle 1) or a patient who discontinues therapy for an IMC-1121B related toxicity during Cycle 1. Patients 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 patients will be treated at the next higher dose level using a dose escalation scheme.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • The patient has had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or patient has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier.
  • The patient has obvious evidence of intratumor cavitation.
  • The patient has undergone major surgery (eg, 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 patient has a history of postoperative bleeding complications or wound complications from a surgical procedure.
  • The patient has elective or planned surgery to be conducted during the trial.
  • The patient has documented and/or symptomatic brain or leptomeningeal metastases. (Patients 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 patient 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 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 patient 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 patient, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005355

Locations
Japan
ImClone Investigational Site
Tokyo, Japan, 104-0045
Sponsors and Collaborators
ImClone LLC
Parexel
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT01005355     History of Changes
Other Study ID Numbers: 13898, CP12-0816, I4T-IE-JVBI
Study First Received: October 5, 2009
Last Updated: September 12, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by ImClone LLC:
Solid tumor
recombinant human IgG1
MAB
 monoclonal antibody
VEGFR 2
human vascular endothelial growth factor receptor 2

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on June 17, 2013