ATNT-22A PHASE 1 STUDY OF TPI 287 CONCURRENT WITH FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) IN TREATMENT OF BRAIN METASTASES FROM ADVANCED BREAST AND NON-SMALL CELL LUNG (NSCL) CANCER

Abstract

BACKGROUND: TPI 287, a member of taxanes diterpenoid (taxoid) family, is a microtubule-stabilizer with significant cytotoxic activity. In vivo studies have demonstrated that TPI 287 penetrates the blood brain barrier and significantly reduces the formation of large brain metastases in models of human breast cancer brain metastasis. The radiosensitizing effect of taxanes has been well established. METHODS: This phase I study (3 + 3 design) explores the safety, recommended phase II dose (RP2D), pharmacokinetics (PK), and antitumor activity (local control rate, distant intra-cranial control rate, progression-free survival) of TPI 287 administered concurrently with FSRT (NCT02187822). Patients with up to 3 untreated brain metastases (maximum diameter of each brain lesion ≤ 5 cm, maximum tumor volume ≤ 120 cc) from breast cancer or NSCLC are eligible. Eligible patients are treated with FSRT to target brain metastases (25 Gy in 5 daily fractions). TPI 287 is administered intravenously once per week, for total of 3 doses. The first dose of TPI 287 is given concurrently with the first fraction of FSRT. Once the RP2D is determined, an additional 10 patients will be enrolled in an expansion safety cohort, for a planned total enrollment of 36 patients. Effect of treatment on quality of life measures will be evaluated. RESULTS: As of June 2015, a total of 4 patients have been enrolled in the first two dose escalation cohorts (14 and 28 mg/m2). No treatment-related grade 3/4 adverse events (AEs) have been observed. No dose limiting toxicity has been reported, and maximal tolerated dose has not been reached. TPI 287 dose escalation continues. CONCLUSIONS: Preliminary data to date indicate that administration of TPI 287 concurrent with FSRT is well tolerated. Updated safety and efficacy results will be presented.