Showing papers by "Barbara A. Goff published in 2017"

Phase Ib study of the mitochondrial inhibitor ME-344 plus topotecan in patients with previously treated, locally advanced or metastatic small cell lung, ovarian and cervical cancers.

Abstract: Background This multicenter, open-label, phase Ib study was designed to assess the safety, pharmacokinetics and preliminary efficacy of ME-344, a mitochondrial inhibitor, administered in combination with the topoisomerase I inhibitor, topotecan, in patients with previously treated, locally advanced or metastatic small cell lung (SCLC), ovarian and cervical cancers. Patients and methods In Part 1, patients received ME-344 10 mg/kg intravenously weekly on days 1, 8, 15 and 22 in combination with topotecan 4 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Cycles were repeated until disease progression or unacceptable toxicity. Patients were evaluated for dose-limiting toxicity (DLT) in cycle 1 and ME-344 pharmacokinetic samples were obtained. In Part 2, patients with locally advanced or metastatic SCLC and ovarian cancer were enrolled in expansion cohorts treated at the recommended phase II dose (RP2D) determined in Part 1. Results Fourteen patients were enrolled in Part 1 and no DLTs were observed. The RP2D of ME-344 in combination with topotecan was established as 10 mg/kg. In Part 2, 32 patients were enrolled. The most common treatment-emergent all-grade and grade 3/4 toxicities included fatigue (65.2%, 6.5%), neutropenia (56.5%, 43.5%) and thrombocytopenia (50%, 23.9%). One patient with recurrent ovarian cancer experienced a partial response by RECIST 1.1 and 21 patients achieved stable disease as best response. Conclusions The combination of ME-344 10 mg/kg weekly and topotecan 4 mg/m2 was tolerable, however, the degree of anti-cancer activity does not support further investigation of the combination in unselected patients with SCLC, ovarian and cervical cancers.

Evaluation of a Validated Biomarker Test in Combination With a Symptom Index to Predict Ovarian Malignancy.

Abstract: Objective This study aimed to evaluate the predictive ability of a multivariate biomarker test in combination with a symptom index (SI) to identify ovarian cancer in a cohort of women planning to undergo surgery for a pelvic mass. Methods This was a prospective study of patients seen at a tertiary care medical center. Following consent, patients completed an SI and preoperative serum was collected for a Food and Drug Administration–cleared multivariate biomarker test [multivariate index assay (MIA)]. Results for the SI and MIA were correlated with operative findings and surgical pathology. Results Of 218 patients enrolled, 124 (56.9%) had benign disease and 94 (43.1%) had borderline tumors or carcinomas. Sixty-six patients had a primary ovarian or fallopian tube cancer. The median age of patients enrolled in this study was 54 years (interquartile range, 44–63 years), of whom 148 (67.9%) were postmenopausal. More than a third (36.3%) of patients with benign masses was accurately identified as low risk by MIA and SI. The sensitivity and negative predictive value (NPV) of the SI relative to primary ovarian cancer was 87.9% (95% CI, 77.9%–93.7%) and 91.6% (95% CI, 84.3%–95.7%), respectively. The sensitivity and NPV of CA125 was 75.4% (95% CI, 63.7%–84.2%) and 86.4% (95% CI, 79.1%–91.5%), respectively, and the sensitivity and NPV of the MIA were 93.9% (95% CI, 85.4%–97.6%) and 94.5% (95% CI, 94.5%–100%), respectively. The overall sensitivity for the combination of MIA plus SI was 100% (66/66; 95% CI, 94.5%–100%), and specificity was 36.3% (45/124; 95% CI, 28.4%–45.0%), with an NPV of 100% (95% CI, 92.1%–100%). Conclusions The addition of a patient-reported SI, which captures subjective symptoms in an objective manner, improved the sensitivity of MIA across all stages and subtypes of ovarian cancer.