Study design and participants
Tumor, toxicity, toxicities, non-melanoma skin cancer, sarcoma, cervical cancer, liver toxicities, Cancers
ADVERSE EFFECTS, BLADDER TUMORS, TUMOR, DISEASE, SARCOMA, CERVICAL CANCER, SECONDARY, GIST, EVENTS, PATHOLOGY, CANCERS
In this phase II trial, adult patients (≥ 18 years) with metastatic KP-wGIST who were naïve of systemic treatment for advanced disease, were enrolled in 15 tertiary, expert sarcoma centers in Spain, France and Italy. Other relevant inclusion criteria were histological confirmation by central pathology review, as well as central molecular confirmation of wild-type condition in Some relevant exclusion criteria were any prior systemic treatment for metastatic GIST. Patients that have received imatinib in an adjuvant setting are eligible only if they have relapsed after a minimum of 2 years from ending treatment with imatinib. Cancers other than GIST within 5 years prior to randomization except for curatively treated cervical cancer in situ, non-melanoma skin cancer, and non-invasive superficial bladder tumors. A protocol amendment allowed for the accrual of patients previously treated with imatinib.Patients received 160 mg (4 × 40 mg film-coated tablets) of regorafenib, once a day for 3 weeks, in 4-week cycles. If dose reduction of regorafenib was necessary because of toxicity, the dose would be reduced stepwise by 40 mg at each step. Two dose-level reductions were considered, 120 mg (-1) and 80 mg (-2) per day. If the subject needed more than 2 dose-level reductions, treatment should be discontinued. If the toxicity was abated with dose reduction up to grade 0 or 1 and, at the discretion of the investigator, was considered safe, the regorafenib dose would then be increased stepwise. Dose interruptions were planned and detailed by the protocol for general toxicities, and specifically for skin, blood pressure and liver toxicities.Treatment with regorafenib was continued until any of the following events occurred: RECIST progression, unacceptable toxicity, patient considered non-compliant with the protocol requirements by the investigator or sponsor, withdrawal of consent, or a delay in regorafenib administration of longer than 4 weeks. Adverse effects were graded according to CTCAE 4.03 and were monitored once every 4 weeks. Radiological assessments of target and non-target lesions were evaluated every 8 weeks by CT scans. Tumor density was determined by indicating the CT attenuation coefficient in Hounsfield units (HU) captured in portal phase. Central radiology review was mandatory at the end of the study. All centers had to upload their CT scans, in an anonymous way, to a web-based imaging platform.The main endpoint was disease control rate (DCR) lasting for at least 12 weeks, and secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) by RECIST 1.1 and Choi criteria, safety and quality of life.