Study of the Safety and Pharmacokinetics of IMC-3G3 in Japanese Patients With Solid Tumors

Metastasis Clinical Trial

Official title:

A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-3G3 Administered in a 2-week, or 3-week Schedule to Japanese Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01199822
• Other study ID #: 13940
• Secondary ID: CP15-090715B-IE-
• Status: Completed
• Phase: Phase 1
• First received: September 8, 2010
• Last updated: February 8, 2012
• Start date: September 2010
• Est. completion date: January 2012

Study information

• Verified date: November 2011
• Source: ImClone LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Participants in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (I.V.) IMC-3G3 once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (one cycle). After the first cycle, patients experiencing an overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive IMC-3G3 at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Solid tumor that has been histopathologically or cytologically documented

• Advanced primary or recurrent solid tumor patient who has not responded to standard therapy or for whom no standard therapy is available

• Measurable or nonmeasurable lesions

• An Eastern Cooperative Oncology Group performance status score of 0-1

• Able to provide informed consent

• Has a life expectancy of > 3 months

• Adequate hematologic function

• Adequate hepatic function

• Has adequate renal function

• Agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy

• Adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with non-approved monoclonal antibodies, a minimum of 8 weeks must have elapsed

• Is willing to comply with study procedures until the End-of-Therapy visit

Exclusion Criteria:

• Received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or has ongoing side effects = Grade 2 due to agents administered more than 28 days earlier

• Has undergone major surgery (eg, laparotomy, thoracotomy, removal of organ[s]) within 28 days prior to study entry

• Elective or planned surgery to be conducted during the trial

• Documented and/or symptomatic brain or leptomeningeal metastases (patients who are clinically stable [no symptoms during the 4 weeks prior to study entry] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)

• Uncontrolled intercurrent illness including, but not limited to:

• Active infection requiring systemic antibiotic treatment excluding oral administration (= Grade 3 [NCI-CTCAE Version 4.02])

• Congestive heart failure (Class III or IV per 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 mm Hg, diastolic blood pressure > 95 mm Hg)

• Cardiac arrhythmia requiring treatment (National Cancer Institute - Common Terminology , or asymptomatic sustained ventricular tachycardia

• Peripheral neuropathy of any etiology = Grade 2 (NCI-CTCAE Version 4.02); or

• Any other serious uncontrolled medical disorder(s) in the opinion of the investigator

• Participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies

• Received any previous treatment with agents targeting the PDGF or PDGFR, approved or non-approved

• Known allergy to any of the treatment components (IMC-3G3, histidine, glycine, sodium chloride, mannitol, or polysorbate)

• If female, is pregnant (confirmed by urine or serum pregnancy test) or lactating

• Known alcohol or drug dependency

• Hepatitis B virus (HBV) antigen-, hepatitis C virus (HCV) antibody-, or human immunodeficiency (HIV) antibody-positive (asymptomatic healthy carriers with detectable HBV-DNA, HCV-RNA may be enrolled into the trial)

• Assessed as inadequate for the study by the investigator

Study Design

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

Related Conditions & MeSH terms

• Malignancy
• Metastasis

Intervention

Biological:
• IMC-3G3
Cohort 1 10 mg/kg i.v., administered on Days 1 and 8, every 3 weeks
• IMC-3G3
Cohort 2 20 mg/kg i.v., administered every 2 weeks
• IMC-3G3
Cohort 3 15 mg/kg i.v., administered on days 1 and 8, every 3 weeks

Locations

Country	Name	City	State
Japan	ImClone Investigational Site	Kashiwa	Chiba

Sponsors (1)

Lead Sponsor	Collaborator
ImClone LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs)		Approximately 16 weeks	Yes
Primary	Number of participants with Serious Adverse Events (SAEs)		Approximately 16 weeks	Yes
Primary	Number of Patients with a Dose- Limiting Toxicity (DLT) in Cycle 1		Approximately 6 weeks	Yes
Secondary	Maximum concentration (Cmax)	Cmax for both dosing schedules (Cohort 2, IMC-3G3 administered every 2 weeks) (Cohorts 1 and 3, IMC-3G3 administered every 3 weeks ) will be evaluated during Cycles 1, 2 and 3	Approximately 16 weeks	No
Secondary	Area under concentration (AUC)	AUC for both dosing schedules (Cohort 2, IMC-3G3 administered every 2 weeks) (Cohorts 1 and 3, IMC-3G3 administered every 3 weeks ) will be evaluated during Cycles 1, 2 and 3	Approximately 16 weeks	No
Secondary	Terminal Half-life (t 1/2)	t 1/2 for both dosing schedules (Cohort 2, IMC-3G3 administered every 2 weeks) (Cohorts 1 and 3, IMC-3G3 administered every 3 weeks ) will be evaluated during Cycles 1, 2 and 3	Approximately 16 weeks	No
Secondary	Clearance (Cl)	Cl for both dosing schedules (Cohort 2, IMC-3G3 administered every 2 weeks) (Cohorts 1 and 3, IMC-3G3 administered every 3 weeks ) will be evaluated during Cycles 1, 2 and 3	Approximately 16 weeks	No
Secondary	Volume of distribution at steady state (Vss)	Vss for both dosing schedules (Cohort 2, IMC-3G3 administered every 2 weeks) (Cohorts 1 and 3, IMC-3G3 administered every 3 weeks ) will be evaluated during Cycles 1, 2 and 3	Approximately 16 weeks	No
Secondary	Serum Anti-IMC-3G3 Antibody Assessment (immunogenicity)		Approximately 16 weeks	No