A Study of IMC-A12 in Advanced Solid Tumors
|ClinicalTrials.gov Identifier: NCT01007032|
Recruitment Status : Completed
First Posted : November 3, 2009
Last Update Posted : May 12, 2015
|Condition or disease||Intervention/treatment||Phase|
|Tumors||Biological: IMC-A12||Phase 1|
Patients in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (I.V.) IMC-A12 every 2 weeks or every 3 weeks for 6 weeks (one cycle). After the first cycle, patients experiencing a best overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive IMC-A12 at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met.
A minimum of three patients will be enrolled in each cohort. The starting dose in Cohort 1 will be 6 mg/kg, administered every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg administered every 2 weeks) will occur once at least three patients in Cohort 1 have completed one cycle of therapy (ie, completed the initial 6 week treatment period or discontinued therapy due to an IMC-A12 -related adverse event [AE]).
Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until all patients have completed one cycle of therapy (as defined above) in Cohort 2. Similarly, patients will be enrolled in Cohort 4 once at least three patients have completed one cycle of therapy in Cohort 3; patients in Cohort 4 will receive 20 mg/kg administered every 3 weeks. Toxicity data for each cohort will be reviewed prior to any dose escalation. No intrapatient dose escalation is permitted. Patients in any cohort who do not complete the first 6 weeks of treatment for reasons other than an IMC-A12 -related toxicity will be replaced.
A dose-limiting toxicity (DLT) is defined as one of the following events, if considered by the investigator to be definitely, probably, or possibly related to IMC-A12 : Grade 4 neutropenia lasting > 7 days; Grade 4 anemia; Grade ≥ 3 thrombocytopenia; Grade ≥ 3 neutropenia associated with fever; Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality and Grade 3 hyperglycemia; Grade 4 hyperglycemia; and/or Grade 4 or uncontrollable hypertension.
If three patients complete the first 6-week cycle (according to the definition outlined above) with no DLTs, dose escalation to Cohort 2 may proceed. If one DLT is observed in the initial three patients of Cohort 1 (or any cohort) during Cycle 1, three additional patients will be enrolled into that cohort. If no additional DLTs are observed, dose escalation may continue as described above.
If two or more patients in Cohort 1 experience a DLT, six patients will be enrolled into Cohort 1A (receiving 4 mg/kg every 2 weeks). If two or more patients experience a DLT in dose Cohort 3, six patients will be enrolled into dose Cohort 3A (10 mg/kg every 3 weeks). If two or more patients experience a DLT in dose Cohorts 2 or 4, six additional patients will be enrolled into the previous cohort (Cohort 1 or Cohort 3, respectively), and the previous cohort will be considered the maximum tolerated dose for that dosing schedule. If two or more patients in any cohort experience a DLT on Week 7 or beyond (after Cycle 1), the data will be reviewed and enrollment may be suspended. The Sponsor and Principal Investigator, with reference to the review of the Independent Data Safety Evaluation Committee (established in a separate document), will determine whether enrollment should resume.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-A12 Administered Every 2 Weeks or Every 3 Weeks to Japanese Patients With Advanced Solid Tumors|
|Study Start Date :||November 2009|
|Primary Completion Date :||December 2012|
|Study Completion Date :||April 2015|
Pts will receive I.V. IMC-A12 every 2 or 3 weeks. A cycle is defined as 6 weeks, with radiological evaluation of tumor response after each cycle. After the 1st cycle, pts with a complete response (CR), PR, or SD will continue to receive IMC-A12 at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met. A minimum of 3 pts will be enrolled in each cohort. The starting dose in Cohort 1 will be 6 mg/kg every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg every 2 weeks) will occur once at least 3 pts in Cohort 1 have completed 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 (as defined above) in Cohort 2. Similarly, pts will be enrolled in Cohort 4 once at least 3 pts have completed once cycle of therapy in Cohort 3; pts in Cohort 4 will receive 20 mg/kg given every 3 weeks.
- Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: 6 months ]Summary listing of Participants Reporting Treatment-Emergent Adverse Events that received IMC-A12.
- Maximum concentration (Cmax) [ Time Frame: 6 months ]Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma after drug infusion
- Area under the Curve (AUC) [ Time Frame: 6 months ]
- Half-life (T1/2) [ Time Frame: 6 months ]
- Drug clearance (CL) [ Time Frame: 6 months ]The rate of elimination proportional to the amount of drug in the body
- Serum Anti-IMC-A12 Antibody Assessment (immunogenicity) Immunogenicity [ Time Frame: 6 months ]Screen for the development of circulating antibodies against IMC-A12
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01007032
|ImClone Investigational Site|
|Kashiwa, Japan, 277 8577|
|Study Director:||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|