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
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
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
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Summary Listing of Participants Reporting Treatment-Emergent Adverse Events
Summary listing of Participants Reporting Treatment-Emergent Adverse Events that received IMC-A12.
E-mail: ClinicalTrials@ ImClone.com
Japan: Ministry of Health, Labor and Welfare