Table 1 describes the characteristics of the patients enrolled on the trial. Eligibility included patients with pathological diagnosis of non-small cell lung cancer (NSCLC) who met one of the following criteria; 1) previously untreated, medically inoperable disease and are to receive radiation therapy to primary disease site; 2) previously resected disease and have relapsed with mediastinal disease; or 3) limited, metastatic disease in no more than one distant site, age > 18, ECOG PS 0 - 2, adequate organ system function, adequate bone marrow function life expectancy of at least 3 months, and informed consent. Additional criteria for inclusion included adequate liver function, adequate renal function, adequate pulmonary function: FEV1 > 1.2 L, and patient ability to swallow pills. Finally, patients with previously treated brain metastases, with or without whole brain radiation therapy, that have been surgically resected or treated with gamma knife and have been stable for 2 months were considered eligible at the discretion of the primary investigator.

Exclusion criteria included a history of NSCLC previously treated with chest radiation, patients who had a serious concurrent uncontrolled medical disorder, patients with uncontrolled or significant cardiovascular disease, including a recent (<6 months) myocardial infarction, any degree of congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias, patients with a history of gastrectomy, pregnant or breast feeding patients, patients who had had prior radiotherapy to the primary tumor site, patients with untreated brain metastases, or patients who had received any investigational agent within 21 days prior to enrollment. Fertile patients were required to use effective birth control. Patients were given a trial information packet and were required to give written informed consent prior to enrollment into the trial. This trial was approved by the UTSW IRB.

Satraplatin was administered daily, initially at 10 mg given five times weekly (50 mg/week), simultaneously with radiotherapy (Monday to Friday) for seven weeks. In subsequent cohorts of patients the dose of Satraplatin treatment was increased from 10 mg/d to 40 mg/d. Dose escalation of Satraplatin was in cohorts of 3 patients. Cohorts were expanded to 6 patients if DLT occurred that was attributable to Satraplatin. All patients received concurrent radiotherapy administered over seven weeks. Those patients who responded to the chemoradiation or had stable disease may have received 3 cycles of consolidation docetaxel chemotherapy at the discretion of the investigator.

Endpoints of the study included determining dose limiting toxicity (DLT), maximum tolerated dose (MTD), and assessment of dose to be recommended for phase 2 trials with Satraplatin and concurrent chest radiation for patients with NSCLC. DLTs were defined as acute grade 4 non-hematologic toxicities or grade 4 hematologic toxicities occurring during concurrent chemoradiation therapy.

Acute non-hematologic toxicity is defined to be a toxicity occurring from day 1 of study entry to day 1 of consolidation chemotherapy or within 60 days from the start of radiotherapy treatment, whichever occurs first. Grade 3 or 4 pneumonitis or esophagitis occurring during the acute phase and/or consolidation phase was also a DLT for this study. Finally, retreatment delay with Satraplatin of >7 days total because of toxicity was considered a DLT. MTD was defined as the dose of drug which causes a DLT in >2 patients. The principal investigator, with the sponsor, was allowed to declare an MTD independent of the above criteria based on their evaluation of patient toxicity. Recommended dosage (RD) was defined as the dose of the drug 1 dose level below MTD. Tumor response was assessed via RECIST criteria.

For each dose level, up to six patients were accrued. After 60 days of evaluation, the current dose was considered acceptable if the first three patients had no toxicity, or less than three of the six patients experienced DLTs. Next, dose escalation involved accruing up to six new patients to the next dose level in the sequence. Otherwise, if three or more patients experienced DLTs, the current dose was considered too toxic, and the preceding dose was declared the MTD. At a given dose level, the probability of halting dose escalation when the true toxicity is 50% or higher is at least 65%. In addition, if the true DLT rate is instead 20%, there will still be a 10% probability of halting dose escalation at a given dose level (type I error). The MTD was defined as that dose level which causes, in three or more of six patients, any DLT and/or at the discretion of the investigator and the sponsor based on the evaluation of any DLT.

Frequency tables with counts and percentages were used to describe pretreatment patient characteristics. Kaplan-Meier analysis was used in evaluating overall survival (OS) and disease free survival outcomes. An event in overall survival was death due to any cause. OS was determined from date of study entry to date of death or last follow-up. This phase 1 trial was not powered to make comparisons of efficacy endpoints between dose levels so only estimates with 95% confidence intervals were presented [25].

The study opened in May 2007 and was closed by May of 2010 after accruing a total of 15 patients who were treated with four different dose levels of Satraplatin and concurrent radiation. Of the 15 patients enrolled, all were eligible and evaluable. Of the 15 patients enrolled in the trial, the median age was 61 (Table 1). 11/15 patients were male and two-thirds of the patients were Caucasian. Four patients had ECOG performance status (PS) of 0, nine with ECOG PS of 1, and one each with ECOG PS of 2 and 3, respectively (Table 1).

Figure 1 summarizes the treatment schema of the trial. Satraplatin was administered orally 1 - 3 hours prior to each radiation treatments: 63Gy/6 - 7 weeks. Dose esca lation of Satraplatin was in cohorts of 3 patients. Cohorts were expanded to 6 patients if DLT occurred that was attributable to Satraplatin. Satraplatin was administered Day 1 - 5 weekly for seven weeks. Consolidation with docetaxel at 75 mg/m² q 21 days × 3 cycles was left to the discretion of the investigator and clinician.