Entry Detail
| General information | |
| Database: | DB00363 |
| Objective: | There is a need to improve the systemic treatment of advanced adenoid cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary investigations of molecularly targeted agents have been disappointing. In this study, they evaluate sorafenib, an oral multikinase inhibitor, which has an attractive targeting profile for this disease. |
| Authors: | Thomson DJ, et al |
| Title: | Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck. |
| Journal: | Head Neck. |
| Year: | 2015 |
| PMID: | 24346857 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced salivary adenoid cystic carcinoma of the head and neck |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II trial |
| Key Patients Feature: | Eligible patients were aged 18 years with histologically confirmed ACC of the head and neck with unresectable locally recurrent and/or metastatic disease. Anynumber of prior therapies were allowed, including chemotherapy, other molecularly targeted agents, radiofrequencyablation, and radiotherapy. however, patients must havecompleted radiotherapy or any systemic treatment morethan 3 or 4 weeks before enrollment, respectively.Other eligibility criteria included: presence of at least 1unidimensional measurable lesion as defined by ResponseEvaluation Criteria in Solid Tumors (RECIST) committeecriteria21; Eastern Cooperative Oncology Group (ECOG)performance status 0 or 122; adequate bone marrowreserve (plt 100 3 109/l; Hb 100 g/l; absolute neutrophil count 1.5 3 109/l), liver function (bilirubin 1.5 3ULN; ALT/AST 2.5 3 ULN [ 5 3 ULN for patientswith liver metastases]; AlkPhos 4 3 ULN, PT, andAPTT <1.5 3 ULN), and renal function (Cr 1.5 3ULN). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients with unresectable locally recurrent and/or metastatic ACC were treated with sorafenib 400 mg bid. |
| Primary End Point: | PFS at 12 months. |
| Secondary End Point: | response rate, time to progression (TTP), OS, and to characterize the toxicity profile. |
| Patients Number: | 23 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | complete response 0/19, partial response 2/19, stable disease 13/19, progressive disease 4/19 |
| Disease Control Rate: | 0.79 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.3 (95% confidence interval [CI], 8.9-13.7) |
| Median OS A vs. C: | 19.6 (CI, 12.4-26.8) months |
| Adverse Event(agent arm): | The most common grade 3 toxicities were fatigue, weight loss, hand foot syndrome, abdominal pain, and deranged liver function tests. A dose reduction was required in 74% of patients (12 of 23 patients were reduced to 600 mg and 5 of 23 to 400 mg) and only 6 of 23 patients did not receive this. Dose intensity, defined as the sum of the total intended dose divided by the sum of the actual total dose received for each patient (including dose reductions, planned treatment interruptions, and reported missed doses) expressed as median and mean percentages was 77% and 79%, respectively. |
| Conclusions: | Sorafenib showed modest activity in ACC with a 12month PFS of 46.2%. Sorafenib 400 mg bid was associated with significant toxicity and, taken together with limited effectiveness, cannot be enthusiastically recommended for further evaluation. |