A Study of IMC-A12 in Advanced Solid Tumors

NCT01007032 | Completed Phase 1 Results DMC

• 4 other identifiers: 1390521-1258CP13-0813I5A-IE-JAEA
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, participants will initially receive intravenous (IV) cixutumumab (IMC-A12) every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing a best overall response of complete response, partial response, or stable disease will continue to receive cixutumumab at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met. Participants will be enrolled at one study center, located in the National Cancer Center Hospital - East, Kashiwa, Japan. Approximately 20-30 participants are anticipated.

Conditions

Tumors

Keywords

anti-IGF-IR; monoclonal; solid tumor; insulin-like growth factor

Outcome Measures

Primary Outcomes (7)

• Summary Listing of Percentage of Participants Reporting Treatment-Emergent Adverse Events

  A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

  Up To 63 Months

• Number of Participants With a Dose Limiting Toxicity (DLT)

  DLTs were defined as any cixutumumab-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events (reported in the subsequent Primary Outcome Measure).

  First Dose Up to 6 Weeks

• Pharmacokinetics (PK): Maximum Concentration (Cmax)

  Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

• PK: Area Under the Curve From Zero to Infinity AUC(0-∞)

  Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

• PK: Area Under Concentration Versus Time Curve During One Dosing Interval (AUCtau)

  Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 Hours Following End of Infusion

• Half-life (t1/2)

  Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 hours) Following End of Infusion

• Drug Clearance (CL)

  Prior to Infusion and Immediately Following End of Infusion (Cohorts 1 and 2) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, and 336 hours and (Cohorts 3 and 4) at 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 408 and 504 hours) Following End of Infusion

Secondary Outcomes (2)

• Number of Participants With Serum Anti-Cixutumumab Antibody Assessment Immunogenicity

  6 months

• Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

  From the First Dose up to 32 Months

Study Arms (1)

Cixutumumab

EXPERIMENTAL

Participants receive IV cixutumumab every 2 or 3 weeks. A cycle equals 6 weeks, with radiological evaluation of tumor response after each cycle. After 1st cycle, pts with a complete response (CR), PR, or SD continue to receive cixutumumab cohort dose and schedule disease progression. 3 pts enroll in each cohort. Starting dose in Cohort 1 is 6 mg/kg every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg every 2 weeks) occurs at least 3 pts in Cohort 1 completes 1 cycle of therapy. Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until at least 3 pts have completed one cycle of therapy in Cohort 2. Pts enroll in Cohort 4 once at least 3 pts have completed once cycle of therapy in Cohort 3; pts in Cohort 4 receive 20 mg/kg every 3 weeks.

Biological: Cixutumumab

Interventions

Cixutumumab BIOLOGICAL

Cixutumumab intravenously

Also known as: IMC-A12, LY3012217

Cixutumumab

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 has been histopathologically or cytologically documented
• Advanced primary or recurrent solid tumor participant who has not responded to standard therapy or for whom no standard therapy is available
• The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) guidelines
• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS)score of 0-1 at study entry
• The participant is able to provide 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/m3 or /μL
• A hemoglobin ≥ 10 g/dL; and
• A platelet count ≥ 100,000/mm3 or /μL
• The participant has adequate hepatic function, as defined by:
• Total bilirubin ≤ 1.8 mg/dL
• Aspartate transaminase (AST) ≤ 2.5 times the upper limit of site-specific normal ranges (five times in case of liver metastasis)
• Alanine transaminase (ALT) ≤ 2.5 times the upper limit of site-specific normal ranges (five times in case of liver metastasis)

You may not qualify if:

• The participant has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the participant has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
• The participant 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 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 the 4 weeks prior to enrollment) with an assessment that no further treatment (radiation, surgical excision, or administration of steroids) is required are permitted to enter the study)
• The participant has an uncontrolled intercurrent illness including, but not limited to:
• Thrombotic or hemorrhagic disorders
• Gross hemoptysis (approximately one-half a teaspoon)
• Ongoing or active infection requiring systemic antibiotic treatment
• 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 (NCICTCAE Version 3.0 Grade 3), or asymptomatic sustained ventricular tachycardia
• Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE Version 3.0); or
• Any other serious uncontrolled medical disorder(s) in the opinion of the investigator
• The participant has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to study entry

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Parexel: collaborator
• Medidata Solutions: collaborator

Study Sites (1)

ImClone Investigational Site

Kashiwa, 277 8577, Japan

Location

Related Publications (1)

• Doi T, Shitara K, Kojima T, Yoshino T, Dontabhaktuni A, Rebscher H, Tang S, Cosaert J, Ohtsu A. A phase I study evaluating cixutumumab, a type 1 insulin-like growth factor receptor inhibitor, given every 2 or 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1253-62. doi: 10.1007/s00280-016-3041-7. Epub 2016 Apr 30.

  PMID: 27139036 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

cixutumumab

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: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2009
• First Posted: November 3, 2009
• Study Start: November 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2015
• Last Updated: February 27, 2019
• Results First Posted: February 27, 2019

Record last verified: 2018-10

Locations

JP (1)