Single-arm trials

In a 24-week open, single-arm trial, 108 antiretroviral therapy-naive, HIV-infected prisoners were given a combination tablet of lamivudine -I- zidovudine (150 mg/300 mg) and a tablet of abacavir 300 mg bd (2). The plasma HIV-1 RNA concentration remained at 400 copies/ml or less in 85% of the patients and at less than 50 copies/ml in 75%. Nausea was the most common adverse effect (n = 40). Four patients withdrew prematurely because of one or more of the following abdominal discomfort and pain abdominal distension neutropenia malaise or fatigue nausea and vomiting. Two patients had a suspected hypersensitivity reaction to abacavir and were withdrawn. 

A total of 222 women with HER2-overexpressing (IHC 2-1- or IHC 3-i-) MBC were enrolled into this multicenter, open-label, single-arm trial of Herceptin as second/third-line monotherapy [51]. All patients had pre-... 

To date, no randomized controlled trial has been complete to provide Level I data supporting the use of mechanical thrombectomy in acute ischemic stroke. However, three large prospective single-arm trials have... 

The Multi-MERCI trial was an international multicenter single-arm trial with the main objective of exploring the safety and efficacy of thrombectomy in patients who fail IV rt-PA. In addition, safety and technical efficacy data for a second-generation retriever were collected [24, 27]. The inclusion/exclusion criteria, techniques, and measures of outcome were otherwise similar to the ones used in the MERCI trial. A total of 177 patients were enrolled in the study. The device was deployed in 164 patients who served as the... 

Nervous system Patients with central nervous system metastases were excluded from bevacizumab trials following a case of fatal cerebral hemorrhage in a patient with hepatocellular carcinoma in 1997. In a retrospective exploratory analysis using datasets from 13 randomized controlled phase II/III trials, 2 open, single-arm trials, and 2 prospective studies in patients with treated nervous system metastases from advanced/ metastatic breast cancer, non-small cell lung carcinoma, and renal and colorectal cancers were at similar risks of cerebral hemorrhage, independent of bevacizumab therapy [96 ]. 

Erbitux has shown its efficacy in recurrent and metastatic HNC as well. A single-arm trial of Erbitux... 

The Interventional Management of Stroke (IMS I) Study was a multicenter, open-labeled, single-arm pilot study in which 80 patients (median NIHSS 18) were enrolled to receive IV rt-PA (0.6 mg/kg, 60 mg maximum, 15% of the dose as a bolus with the remainder administered over 30 minutes) within 3 hours of stroke onset (median time to initiation 140 minutes). " Additional rt-PA was subsequently administered via a microcatheter at the site of the thrombus in 62 of the 80 patients, up to a total dose of 22 mg over 2 hours of infusion or until complete recanalization. Primary comparisons were with similar subsets of the placebo and rt-PA-treated subjects from the NINDS rt-PA Stroke Trial. The 3-month mortality in IMS I subjects (16%) was numerically lower but not statistically different than the mortality of the placebo (24%) or rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic ICH (6.3%) in IMS I subjects was similar to that of the rt-PA-treated subjects (6.6%) but higher than the rate in the... 

The MERCI trial was a prospective single-arm, multicenter trial designed to test the safety and efficacy of the MERCI clot retrieval device to restore the patency of intracranial arteries in the first 8 hours of an acute stroke. All patients were ineligible for IV rt-PA. The occlusion sites were the intracranial vertebral artery, basilar... 

The Penumbra stroke system (Penumbra Inc., San Leandro, CA) includes two different revascularization options (1) thrombus debulking and aspiration may be achieved by a reperfusion catheter that aspirates the clot while a separator device fragments it, and (2) direct thrombus extraction may be performed by a ring retriever while a balloon guide catheter is used to temporarily arrest flow. This system has been tested in a pilot trial in Europe. Twenty patients (mean NIHSS 21) with a total of 21 vessel occlusions (7 ICA, 5 MCA, and 9 Basilar) were treated up to 8 hours after symptom onset. Recanalization prior to lA lysis was achieved in all cases (48% TIMI 2 52% TIMI 3). Seven patients were also treated with lA UK or rt-PA. Good outcome at 30 days (defined as mRS < 2 or NIHSS 4-point improvement) was demonstrated in 42%. The mortality rate was 45%, but there were no device-related deaths. There was one asymptomatic SAH and three symptomatic ICHs. A prospective, single-arm, multicenter trial is being conducted in the United States and Europe currently. 

Randomized Controlled Trial PSAS Prospective Single-Arm Study sICH symptomatic intracranial hemorrhage lAT number of patients treated with intra-arterial thrombolysis Primary end point (90-day mRS <2) was reached (p = 0.04)... 

The Pennmbra Stroke Trial was a prospective, single-arm, mnlticenter trial conducted at 24 international centers in the U.S. and Enrope [87]. Inclusion/excln-sion criteria were roughly similar to the ones nsed in the MERCI and Multi-MERCI trials including stroke signs/symptoms with baseline NIHSS >8, symptom dnration between 0 and 8 h, and occlnsion of a treatable vessel on angiography. A total of 125 patients were emolled (mean age, 63.5 13.5 years mean baseline NIHSS, 17.3 5.2 49% female median time from stroke onset to procedure, 4.1 h). The occlusion sites were the ICA (18%), Ml or M2 MCA branches (70%), vertebro-basilar arteries (9%), and other (3%). 

A complete response in heavily pretreated relapsed or resistant AML patients was seen in 26% of 277 patients treated in a pivotal, open-label, single-arm Phase II trial. About half of the patients failed to recover normal platelet numbers, but were asymptomatic and transfusion free. Recurrence-free survival was 5.5 months. Gem Ozo was approved by the FDA in May 2000 for use in patients with CD33-positive AML in first relapse who are 60 years of age or older and are not candidates for cytotoxic chemotherapy. A significant advantage of Gem Ozo is the reduced toxicity versus traditional chemotherapy, which allows many patients to be treated on an out-patient basis, reducing hospitalization costs. 

A prospective, open-label, single-arm, multicenter trial (n=159) in Italy tested the efficacy of deferasirox (20mg/kg/day, followed by titration in response to serum ferritin levels) in the treatment of transfusion-dependent patients with myelodysplastic syndromes [20 ]. Eighty-four patients discontinued deferasirox treatment 22 died and 28 withdrew due to an adverse event. Adverse events were cardiac (1), ocular (1), GI (54), general disorders and administration site conditions (1), hepatobiliary (5), investigations (14), metabolism and nutrition (3), renal and urinary (15) as well as skin and subcutaneous (SC) (6). 

Nolte F, Hochsmann B, Giagounidis A, Lubbert M, Platzbecker U, Haase D, et al. Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload. Ann Hematol January 2013 92(2) 191-8. 

Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, GiannareUi D, et aL Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma an open-label, single-arm, phase 2 trial. Lancet Oncol 2013 14(11) 1104-11. 

A preliminary assessment of the effect of food on pharmacokinetics can generally be studied in a single-dose, two-arm, randomised, crossover design. Preliminary information can often be obtained by including a fed occasion in the first, dose-escalating study. This will be insuffi-cent for registration purposes, which require an adequately powered study performed with the final formulation, but the information should be sufficient to indicate whether there is need for restrictions on dosing relative to meals in repeat-dose studies in healthy volunteers and patient clinical trials. 

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