| General information |
| Database: | DB00272 |
| Objective: | Thisphase I, dosefinding study determined the safety, maximum tolerated dose (MTD)/recommendedphase 2 dose (RP2D), and antitumor activity of PX866, a phosphatidylinositol 3kinase inhibitor, combined with cetuximab in patients with incurable colorectal cancer or squamous cell carcinoma of the head and neck. |
| Authors: | Bowles DW, et al |
| Title: | A multicenterphase 1 study of PX866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24916771 |
| Trial Design |
| Clinical Trial Id: | NCT01152628 |
| Agent: | PX866
|
| Target: | PI3K gamma
|
| Cancer Type: | colorectal cancer or head and neck cancer |
| Cancer Subtype: | advanced colorectal carcinoma or advanced squamous cell carcinoma of the head and neck |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | PX866+ cetuximab |
| Study Type: | a phase I, dosefinding study |
| Key Patients Feature: | metastatic KRAS codon 12 and 13 wildtype CRC or recurrent/metastatic HNSCC; measurable disease per RECIST 1.1; life expectancy > 3 months; adequate hepatic, hematologic, and renal function; magnesium more than and equal to lotheyr limit of normal; |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | PX866 was administered at escalating doses (68 mg daily) combined with cetuximab given at a 400 mg/m(2) loading dose followed by 250 mg/m(2) weekly. A "3 + 3" study design was used. Prior therapy with antiEGFR therapies, including cetuximab, was allowed. |
| Primary End Point: | maximal tolerated dose (MTD)/RP2D, toxicity profile, pharmacokinetics, antitumor activity, and predictive biomarkers of response |
| Secondary End Point: | NA |
| Patients Number: | 11 |
| Trial Results |
| DLT_MTD: | No dose limiting toxicities were observed. The RP2D was 8 mg, the same as the singleagent PX866 MTD. |
| Objective Response Rate: | Best responses in 9 evaluable patients were: 4 partial responses (44.4%), 4 stable disease (44.4%), and 1 disease progression (11.1%). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 106 days (range: 1271) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent treatmentemergent adverse event was diarrhea (90.1%), followed by hypomagnesemia (72.2%), vomiting (72.2%), fatigue (54.5%), nausea (54.5%), rash (45.5%) and peripheral edema (40%). |
| Conclusions: | Treatment with PX866 and cetuximab was tolerated with signs of antitumor activity. Further development of this combination is warranted. |