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