| General information |
| Database: | DB00677 |
| Objective: | The aim of thisphase 1 study was to assess the safety, tolerability, and pharmacokinetics of RRx001. |
| Authors: | Reid T, et al |
| Title: | Safety and activity of RRx001 in patients with advanced cancer: a firstinhuman, openlabel, doseescalationphase 1 study. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26296952 |
| Trial Design |
| Clinical Trial Id: | NCT01359982 |
| Agent: | RRx001
|
| Target: | Free radicals
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a firstinhuman, openlabel, doseescalationphase I study |
| Key Patients Feature: | Eligible patients were 18 years or older withhistologically confirmed advanced solid tumours forwhich standard curative treatment did not exist. Allpatients had an Eastern Cooperative Group performancestatus of 2 or less, an estimated life expectancy of at least12 weeks, and adequate laboratory parameters (absoluteneutrophil count more than and equal to 1 5 ¡Á 10 cells per L, platelet countmore than and equal to 7 5 ¡Á 10 cells per L, haemoglobin more than and equal to 90 g/L, serum totalbilirubin less than and equal to 427 5 ¦Ìmol/L, aspartate amino transferase andalanine aminotransferase concentration less than and equal to 2 5 times theupper normal limit [ULN; <5 times the ULN for hepaticinvolvement], and creatinine clearance >50 mL per min).Previous antineoplastic therapies had to have beendiscontinued at least 6 weeks before intervention start, and patients could show no residual sideeffects ofprevious therapies. Patients were required to practiseeffective contraception while receiving RRx001. Allpatients had evaluable disease. (Tumour typesColorectalHepatocellular carcinoma MelanomaHead and neck Pancreatic Ovarian CholangiocarcinomaLung Oligodendroglioma) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | 25 patients and treated six patients in the 10 mg/m(2) cohort, three patients in the 16.7 mg/m(2) cohort, three patients in the 24.6 mg/m(2) cohort, four patients in the 33 mg/m(2) cohort, three patients in the 55 mg/m(2), and six patients in the 83 mg/m(2) cohort |
| Treatment Info: | Patients were assigned to receive intravenous infusions of RRx001 at increasing doses (10 mg/m(2), 16.7 mg/m(2), 24.6 mg/m(2), 33 mg/m(2), 55 mg/m(2), and 83 mg/m(2)) either once or twiceweekly for at least 4 weeks, with at least three patients per dose cohort and allowing a 2week observation period before dose escalation. Samples for safety and pharmacokinetics analysis, including standard chemistry and haematological panels, were taken on each treatment day. |
| Primary End Point: | safety, tolerability, and doselimiting toxic effects, singledose pharmacokinetics, and a recommended dose for phase 2 trials |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | a dose of 16.7 mg/m(2) was recommended as the targeted dose forphase 2 trials |
| Objective Response Rate: | Of the 21 evaluable patients, one (5%) patient had a partial response, 14 (67%) patients had stable disease, and six (29%) patients had progressive disease; all responses were across a variety of tumour types. |
| Disease Control Rate: | 0.72 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 17.8 months (95% CI 10.0-not reached) |
| Adverse Event(agent arm): | Pain at the injection site, mostly grade 1 and grade 2, was the most common adverse event related to treatment, experienced by 21 (84%) patients. Other common drugrelated adverse events included arm swelling or oedema (eight [32%] patients), and vein hardening (seven [28%] patients). No doselimiting toxicities were observed. |
| Conclusions: | RRx001 is a welltolerated novel compound without clinically significant toxic effects at the tested doses. Preliminary evidence of activity is promising and, on the basis of all findings, a dose of 16.7 mg/m(2) was recommended as the targeted dose forphase 2 trials. |