Tumor Treating Fields for Locally Advanced NSCLC

NCT06124118 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: HCI166135
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period

  To assess the safety of Tumor Treating Fields (TTFields) started concurrently with SOC chemoradiation and during consolidation durvalumab for treatment of unresectable stage III non-small cell lung cancer (NSCLC).

  12 weeks

Secondary Outcomes (3)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment

  1 year 6 months

• Progression-free survival as defined as the time from CRT to the time documented disease progression (as assessed by RECIST 1.1) or death from any cause.

  1 year 6 months

• Overall survival (OS) as defined as the time from CRT until death from any cause.

  1 year 6 months

Study Arms (2)

Device Duration Level 1

EXPERIMENTAL

Participants in Device Duration Level 1 will receive Tumor Treatment Fields (TTF) therapy during standard of care consolidation durvalumab.

Device: NovoTTF-200T (TTFields) System; Drug: Durvalumab

Device Duration Level 2

EXPERIMENTAL

Participants in in Device Duration Level 2 will begin TTF therapy during SOC durvalumab and SOC Concurrent chemoradiation following Device Duration Level 1.

Radiation: carboplatin chemotherapy; Device: NovoTTF-200T (TTFields) System; Drug: Durvalumab

Interventions

carboplatin chemotherapy RADIATION

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.

Also known as: paclitaxel, nab-paclitaxel

Device Duration Level 2

NovoTTF-200T (TTFields) System DEVICE

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.

Device Duration Level 1; Device Duration Level 2

Durvalumab DRUG

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.

Also known as: Imfinzi

Device Duration Level 1; Device Duration Level 2

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 surgery will be considered to have unresectable disease.
• Able to operate the NovoTTF-200T System independently or with the help of a caregiver.
• Eligible to receive standard of care chemoradiation per institutional standards.
• Subject must have measurable disease by RECIST 1.1 criteria by CT.
• ECOG Performance Status ≤ 1.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10 g/dL (transfusions are allowed for Device Duration Level 2 only if anemia is due to prior therapy.)
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) or direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN.
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
• Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.

You may not qualify if:

• Prior thoracic radiation, including breatbreast radiation.
• Prior exposure to TTFields.
• Prior systemic immunotherapy or radiotherapy for NSCLC.
• nown underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel.
• Known hypersensitivity to radiation due to genetic susceptibility, connective tissue disease, or any other cause.
• Receiving other investigational agents.
• Major surgery (per treating investigator) within 4 weeks prior to starting study drug or who have not fully recovered from major surgery. Note: Biopsies without significant complications will not be considered major surgery.
• The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6).
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious or clinically significant cardiac arrhythmias.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
• QTc prolongation defined as a QTcF \> 500 ms.
• Known congenital long QT.
• Left ventricular ejection fraction \< 50%.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; 130-nm albumin-bound paclitaxel; Drug Delivery Systems; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Drug Therapy; Therapeutics

Study Officials

• Matthew Gumbleton, MD, PhD

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kaitlin Stephens

CONTACT

801-213-8494; kaitlin.stephens@hci.utah.edu

Matthew Gumbleton, MD, PhD

CONTACT

801-587-4470; matthew.gumbleton@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Bayes optimal interval design (BOIN)

Study Record Dates

• First Submitted: November 3, 2023
• First Posted: November 9, 2023
• Study Start: April 4, 2024
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)