| General information |
| Database: | DB00803 |
| Objective: | AZD2171 is a potent inhibitor of vascular endothelial growth factor receptors that showed broad antitumor activity in preclinical models. Doses of up to 45 mg/d of AZD2171 are tolerable when administered alone. This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non small cell lung cancer. |
| Authors: | Laurie SA, et al |
| Title: | Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non small cell lung cancer: the National Cancer Institute of Canada clinical trials group. |
| Journal: | J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18398152 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cediranib
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | AZD2171+ carboplatin + paclitaxel |
| Study Type: | Phase I and pharmacokinetic study |
| Key Patients Feature: | Eligible patients had advanced, incurable non small cell lung cancer (stage IV, or IIIB with effusion or unsuitable for chemoradiotherapy), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, adequate hematology (CBC) and organ function, and no more than one prior singleagent (nontaxane) chemotherapy (prior adjuvant or neoadjuvant chemotherapy was permitted if completed > 6 months before enrollment). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Eligible patients received carboplatin targeted to an area under the concentration time curve of 6 mg . min/mL and paclitaxel 200 mg/m(2), both on day 1 of a 3week cycle; daily oral AZD2171 at either 30 mg or 45 mg commenced day 2 of cycle 1. Pharmacokinetics of all drugs were performed, and tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). |
| Primary End Point: | the recommended phase II dose (RP2D) |
| Secondary End Point: | the toxicity and pharmacokinetics (PK) profile, and antitumor activity. |
| Patients Number: | 20 |
| Trial Results |
| DLT_MTD: | DLT was defined as the following AZD2171related toxicities in cycle 1: grade 3 or worse renal toxicity, fatigue or handfoot syndrome; delay of cycle 2 chemotherapy by 14 days or longer; grade 4 hypertension or uncontrollable grade 3 hypertension; and an increase in severity or frequency of the expected toxicity of chemotherapy.In the first three patients at 30 mg, one possible but equivocal DLT (grade 3 fatigue) was observed; this was felt multifactorial¡ªopioids, disease progression, and possibly AZD2171. Three additional patients were enrolled with one DLT (grade 3 fatigue, dizziness and ALT increase). Because one of the two observed DLTs was equivocal, three further patients were enrolled to explore this dose level, without further observed DLT. |
| Objective Response Rate: | 45% |
| Disease Control Rate: | 55% |
| Median Time to Progression: | 7.6 months (range, 0.99 to 16.4 months). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | the most common were fatigue, hypertension, diarrhea, mucositis, and anorexia. The 45mg cohort experienced more severe fatigue and diarrhea and more common hoarseness, headache, and thrombotic events. |
| Conclusions: | AZD2171 can be combined with standard doses of carboplatinpaclitaxel with encouraging antitumor activity. Toxicity is increased, but predictable and manageable. |