| General information |
| Database: | DB00357 |
| Objective: | Thisphase I doseescalation study (NCT01295632) aimed to define the doselimiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK0752 (1800 mg once weekly) in patients with solid tumours. |
| Authors: | PihaPaul SA, et al |
| Title: | Results of a phase 1 trial combining ridaforolimus and MK0752 in patients with advanced solid tumours. |
| Journal: | Eur J Cancer. |
| Year: | 2015 |
| PMID: | 26199039 |
| Trial Design |
| Clinical Trial Id: | NCT01295632 |
| Agent: | ridaforolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | ridaforolimus and MK0752 |
| Study Type: | international, multicentre, openlabel, nonrandomised, phase I study |
| Key Patients Feature: | Adult (P18 years old) male or female patients wereeligible for the study if they had histologically confirmedmetastatic or locally advanced solid tumours that hadfailed to respond to standard therapy, that had progressed despite standard therapy, or for which standardtherapy does not exist |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK0752 (1800 mg once weekly) in patients with solid tumours. No intrapatient dose escalation was permitted. |
| Primary End Point: | DLT rate; |
| Secondary End Point: | response rate. |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | one DLT (grade 2 stomatitis, second episode) was reported. Among eight evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade 3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week+1800 mg weekly MK0752. The most common drugrelated adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. |
| Objective Response Rate: | Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response and one with partial response. In addition, one patient experienced stable disease 6 months.Combined ridaforolimus and MK0752 showed activity in HNSCC. however, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development. |
| Disease Control Rate: | 0.13 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common drugrelated adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. |
| Conclusions: | Combined ridaforolimus and MK0752 showed activity in HNSCC. Hotheyver, a high number of adverse events they were reported at the MTD, which would require careful management during future clinical development. |