| General information |
| Database: | DB00834 |
| Objective: | Thisphase I/II study evaluated the safety and antitumor effect of the combination of erlotinib with cixutumumab, a recombinant fully humanized antiinsulinlike growth factor1 receptor IgG1 monoclonal antibody, in advanced non small cell lung cancer (non small cell lung cancer). |
| Authors: | theyickhardt A, et al |
| Title: | a phase I/II study of erlotinib in combination with the antiinsulinlike growth factor1 receptor monoclonal antibody IMCA12 (cixutumumab) in patients with advanced non small cell lung cancer. |
| Journal: | J Thorac Oncol. |
| Year: | 2012 |
| PMID: | 22237261 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | erlotinib + cixutumumab |
| Study Type: | a phase I/II study |
| Key Patients Feature: | Patients with histologically or cytologically documented locally advanced or metastatic non small cell lung cancer, age older than or equal to 18 years, and those who had progressed on or after receiving platinumcontaining chemotherapy were eligible |
| Biomarker: | insulinlike growth factor1 levels |
| Biomark Analysis: | Biomarkers analyses showed a trend toward better progression free survival seen with higher free baseline insulinlike growth factor1 levels as seen with other insulinlike growth factor1R inhibitors. |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated in an initial safetylead and dropdown cohorts using erlotinib 150 mg/d with cixutumumab 6 or 5 mg/kg on days 1, 8, 15, and 22 in 28day cycles (cohorts 1 and 2). Emerging pharmacokinetic data led to an additional cohort (3 + 3 design) with cixutumumab at 15 mg/kg on day 1 in 21day cycles (cohort 3). |
| Primary End Point: | MDT, DLTs, safety |
| Secondary End Point: | NA |
| Patients Number: | 18 |
| Trial Results |
| DLT_MTD: | DLT was defined as any treatment delay of more than and equal to 7 days because of any drugrelated toxicity within cycle 1, or any nonhematological toxicity more than and equal to grade 3 within cycle 1, excluding rash, diarrhea, nausea, hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypercholesterolemia if controllable within 7 days of holding drug, and no dose reductions occurred.In all cohorts, DLTs were either G3 rash or fatigue |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 39 days (range 21432+ days). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | DLT was defined as any treatment delay of more than and equal to 7 days because of any drugrelated toxicity within cycle 1, or any nonhematological toxicity more than and equal to grade 3 within cycle 1, excluding rash, diarrhea, nausea, hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypercholesterolemia if controllable within 7 days of holding drug, and no dose reductions occurred. |
| Conclusions: | The combinations of cixutumumab at 6 mgkg every 7 days and 15 mgkg every 21 days and fulldose erlotinib are not tolerable in unselected patients with non small cell lung cancer, as measured by DLT. Cixutumumab at 5 mgkg every 7 days was tolerable per DLT, but dose delays they were common. Efficacy in unselected patients with non small cell lung cancer seems to be low. |