| General information |
| Database: | DB00266 |
| Objective: | Platinumbased therapy combined with cetuximab is standard firstline therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. They conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN. |
| Authors: | Saba NF, et al |
| Title: | Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck. |
| Journal: | Cancer. |
| Year: | 2014 |
| PMID: | 25103371 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | everolimus+ cetuximab + carboplatin |
| Study Type: | a phase I and pharmacokinetic study |
| Key Patients Feature: | Patients (age more than and equal to 18 years) had previously untreated, unresectable recurrent or metastatic squamous cell carcinoma of the head and neck not amenable to radiotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2;(male/female = 18/2);the median age was 65 years (4475 years). |
| Biomarker: | pmTOR, pAkt, pGSK3¦Á/¦Â, pp44/42 |
| Biomark Analysis: | There was a significant correlation between tumor pp44/42 staining and response (P = .044) and a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received carboplatin (area under the curve = 2 mg/ml/min; 3 weeks on, 1 week off), cetuximab (with a loading dose of 400 mg/m(2) and then 250 mg/m(2) weekly), and doseescalating everolimus (2.5, 5.0, 7.5, and 10 mg/day) with a 3+3 design. After 4 cycles, patients without progression continued cetuximab/everolimus until progression or intolerable toxicity. |
| Primary End Point: | the maximum tolerated dose (MTD), doselimiting toxicities (DLTs), and pharmacokinetics (PK); |
| Secondary End Point: | the estimation of the progression free survival (PFS) and response rate (RR) |
| Patients Number: | 20 |
| Trial Results |
| DLT_MTD: | Two of 6 patients receiving 2.5 mg/day experienced doselimiting toxicity (DLT) with grade 3 hyponatremia and nausea. In 7 patients receiving deescalated everolimus (2.5 mg every other day), grade 3 hyperglycemia produced DLT in 1 of 6 patients. MTD: everolimus with cetuximab and carboplatin was 2.5 mg every other day. |
| Objective Response Rate: | The objective response rate (RR) was 61.5% (all partial responses).There was a significant correlation between tumor pp44/42 staining and response (P = .044) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.15 months |
| Median OS A vs. C: | a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival |
| Adverse Event(agent arm): | NA |
| Conclusions: | The maximum tolerated dose of everolimus with cetuximab and carboplatin was 2.5 mg every other day. The regimen was associated with an encouraging RR and PFS, and this suggested possible clinical efficacy in a select group of patients with squamous cell carcinoma of the head and neck. |