Non Small Cell Lung Cancer
Conditions
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.
Interventions
RADIATIONcarboplatin 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.
DEVICENovoTTF-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.
DRUGDurvalumab
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.
Sponsors
University of Utah
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Bayes optimal interval design (BOIN)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
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 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. * Renal: * Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: * Males: * ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72) * Females: * (((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72))×0.85 * For subjects of childbearing potential: * Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Subjects \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or * Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Subjects ≥ 50 years of age: * Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago; or * Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). * Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 4.6. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Step 2: Pre-Consolidative Immunotherapy Phase Inclusion Criteria * The subject must have previously completed and been eligible for Step 1 registration. * Completion of post-chemoradiation CT scan and RECIST 1.1 assessment. * Eligible to receive consolidation immunotherapy per institutional standards and Investigator judgement. * Able to operate the NovoTTF-200T System independently or with the help of a caregiver. * 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 with concurrent chemoradiation.) * 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. * Renal: * Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: * Males: * ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72) * Females: * (((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72))×0.85 * Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy (except for alopecia or fatigue) unless considered clinically not significant and/or stable by the treating investigator. * Resolution of any pneumonitis from prior radiation therapy to \< grade 1 per the treating investigator.
Exclusion criteria
Step 1: Pre-Chemoradiation Phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period | 12 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | To assess the safety and tolerability of TTFields started concurrently with SOC chemoradiation and during consolidation Durvalumab for treatment of unresectable stage III NSCLC. |
| 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 | To assess progression-free survival (PFS) |
| Overall survival (OS) as defined as the time from CRT until death from any cause. | 1 year 6 months | To assess overall survival (OS) in this study population |
Countries
United States
Contacts
Primary ContactKaitlin Stephens
Backup ContactMatthew Gumbleton, MD, PhD
Outcome results
None listed