A Feasibility Study to Evaluate the Addition of Tumor Treating Fields to Treatment of Locally Advanced Stage III NSCLC

University of Utah

Summary

The goal of this open-label, Phase 1 clinical trial is to determine the safety of TTFields started concurrently with SOC chemoradiation and during consolidation durvalumab in locally advanced, unresectable stage III non-small cell lung cancer (NSCLC). The main question it aims to answer is, "What is the rate of dose-limiting toxicities (DLTs) with TTFields in addition to concurrent chemoradiation and consolidation durvalumab?" Step 1 * All participants will be screened and enrolled in Step 1 prior to SOC concurrent chemoradiation. * The purpose of the Step 1 Registration is to ensure that eligible participants are candidate for concurrent chemoradiation and do not have contraindications to TTF therapy or immunotherapy. * Starting Level: Participants in Device Duration Level 1 will receive standard of care concurrent chemoradiation following Step 1 Registration. * Escalation Level : Participants in Device Duration Level 2 will begin standard of care chemoradiation and treatment with TTFields following Step 1 Registration. Step 2 * All participants will complete Step 2 screening and enrollment prior to receiving treatment with durvalumab consolidation therapy and TTFields. * The purpose of the Step 2 registration is to ensure that eligible patients meet criteria for consolidation durvalumab after completion of CRT and do not have contraindications to TTF. therapy or immunotherapy.

Eligibility

Age range: 22+ years
Sex: All
Healthy volunteers: No

Detailed criteria

Inclusion Criteria: Step 1: Pre-Chemoradiation Inclusion Criteria * Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC). * Clinical AJCC (AJCC, 8th ed.) stage IIIA or IIIB, or IIIC NSCLC with unresectable disease. Staging FDG-PET/CT and MRI brain (preferred) or CT head with contrast scan must have been completed within 60 days prior to initiation of concurrent CRT. Unresectable disease must be determined by a multi-disciplinary team unless, in the opinion of the treating investigator, the subject's disease is clearly unresectable. Subjects who refuse sur…

Interventions

Radiation

carboplatin chemotherapy

Concurrent chemoradiation will be given per standard of care within 24 hours of initiation of standard of care radiation therapy. Treatment will include a paclitaxel/carboplatin chemotherapy regimen administered during the radiotherapy course (over 6-7 weeks). Paclitaxel (50 mg/m2) will be administered intravenous over 1 hour followed by Carboplatin AUC = 2 mg/min/mL intravenous weekly (every 7 days ± 3 days) during radiotherapy 11, NCCN Non-small cell lung cancer guidelines 2023). If a patient has a hypersensitivity reaction to weekly paclitaxel, weekly nab-paclitaxel is allowed to replace paclitaxel at the discretion of the treating medical oncologist 37. The recommended starting dose of weekly nab-paclitaxel is 40 mg/m2 to 50 mg/m2 38 39. Standard premedications with steroids, diphenhydramine, H2 receptor antagonist, and 5-HT3 receptor antagonist antiemetics must be administered per individual institutional guidelines.

Device

NovoTTF-200T (TTFields) System

The NovoTTF-200T (TTFields) System is an investigational medical device delivering 150 kHz TTFields to the thorax for the treatment of patients at the age of 22 years or older. The device is a portable, battery operated system which delivers TTFields at 150 kHz to the thorax by means of insulated Transducer Arrays. The NovoTTF-200T produces electric forces intended to disrupt cancer cell division. TTFields at 150 kHz to the thorax will be continuous for at least 11 hours a day on average, with a recommended duration of at least 18 hours a day. Subjects may take breaks for personal needs (e.g. showering, array exchange). TTFields may be continued as long as there is no disease progression per RECIST 1.1 or any of the treatment discontinuation conditions for subject withdrawal or termination.

Drug

Durvalumab

Consolidation Durvalumab will be given per standard of care and institutional guidelines every 4 weeks for up to 12 cycles. Refer to package insert for detailed pharmacologic, dosing, and safety information.

Summary

Eligibility

Interventions

Location