Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509

IntroductionMalignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.MethodsPatients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.ResultsFifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.ConclusionCediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib

Negotiating for Success: Navigating the Contracting Process for an Exemplary Research Program

Developing successful contracts is imperative for research sites conducting company-sponsored or investigator-initiated clinical trials. Good contracts help ensure sustainability and guide how research will be conducted

A phase I study of the combination of TZT-1027 (soblidotin) and gemcitabine administered on day 1 and 8 every three weeks to patients with advanced or metastatic solid tumors

Background: TZT-1027 is a dolastatin 10 analog interfering with microtubule assembly, with increased antitumor activity when combined with gemcitabine in animal models. Patients and Methods: Eligible patients with refractory solid tumors received gemcitabine followed by TZT-1027 on Days 1 and 8 every 21 days, with pharmacokinetic sampling during the first 24 hours. Results: Fourteen patients received at least one course of study drug (10 at TZT-1027 dose 1.6 mg/m2 and 4 at 2.0 mg/m2). There were 36% male, median age 59 years, median PS 0, median number of prior treatments 2. Reasons for withdrawal included: progression of disease (n=12) and adverse events (n=2). A total of 66 courses were administered. Of 12 instances of dose delay, 8 were due to neutropenia. Grade 3/4 adverse events included neutropenia (50%), thrombocytopenia (14%), fatigue (14%), and anorexia (7%). Cmax and AUCinf were 181 mcg/L (CV% 38.2) and 537 ng.h/mL (n=10 in cohort 1), and peaked at 1.05 hours after the end of TZT-1027 infusion, with a biphasic elimination. T1/2 was 5.12 h, clearance 3.9 L/h/m2, and VSS 16.5 L/m2. Conclusions: The recommended phase II dose is 1.6 mg/m2 of TZT and 800 mg/m2 of gemcitabine. Pharmacokinetics are consistent between studies.C. F. Verschraegen, H. Raftopoulos, K. Feit, R. De Jager, S. Joon Lee & C. Sweene