tumor treating fields for locally advanced nsclc

Conditions: Non Small Cell Lung Cancer

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 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 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 exclusion criteria * 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%. * uncontrolled hypertension defined as persistent blood pressure of ≥ 160/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * implanted pacemaker, defibrillator or other electrical medical devices; * any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.) * known hiv infection with a detectable viral load within 6 months of the anticipated start of treatment. note: subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. * active known infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tb testing in line with local practice), hepatitis b (known positive hbv surface antigen (hbsag) result), or hepatitis c. note: subjects with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody \[anti-hbc\] and absence of hbsag) are eligible. subjects positive for hepatitis c (hcv) antibody are eligible only if polymerase chain reaction is negative for hcv rna. * medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * history of allogenic stem cell or solid organ transplantation * active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or crohn's disease\], systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome \[granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, uveitis, etc.\]). the following are exceptions to this criterion: * patients with vitiligo or alopecia * patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy) * any chronic skin condition that does not require systemic therapy * patients without active disease in the last 5 years may be included but only after consultation with the principal investigator. * patients with celiac disease controlled by diet alone * current or prior use of immunosuppressive medication within 14 days of cycle one day one, except for the following permitted steroids: * intranasal, inhaled, topical steroids, eye drops, or local steroid injection (e.g., intra-articular injection); * systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent; * steroids as premedication for hypersensitivity reactions (e.g., computed tomography (ct) scan premedication). * subjects taking prohibited medications as described in section 5.11. a washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment. * history of exudative pleural effusions, regardless of cytology. * peripheral neuropathy \> grade 1 for patients receiving concurrent carboplatin and paclitaxel with radiation. step 2 pre-consolidative immunotherapy phase exclusion criteria * subjects who in the investigators opinion had disease progression following concurrent chemoradiation. * known underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel. * major surgery (per treating investigator) 4 weeks prior to starting study drug or who have not fully recovered from major surgery. * 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%. * uncontrolled hypertension defined as persistent blood pressure of ≥ 160/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * implanted pacemaker, defibrillator or other electrical medical devices; * any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.) * medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * history of allogenic stem cell or solid organ transplantation * active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or crohn's disease\], systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome \[granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, uveitis, etc.\]). * the following are exceptions to this criterion: * patients with vitiligo or alopecia * patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy) * any chronic skin condition that does not require systemic therapy * patients without active disease in the last 5 years may be included but only after consultation with the principal investigator * patients with celiac disease controlled by diet alone. * current or prior use of immunosuppressive medication within 14 days of cycle one day one, except for the following permitted steroids: * intranasal, inhaled, topical steroids, eye drops, or local steroid injection (e.g., intra-articular injection) * systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent * history of exudative pleural effusions, regardless of cytology.