Clinical trial NCT06124118: Tumor Treating Fields for Locally Advanced NSCLC
Official title: A Feasibility Study to Evaluate the Addition of Tumor Treating Fields to Treatment of Locally Advanced Stage III NSCLC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 30
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Bayes optimal interval design (BOIN)
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period
timeFrame: 12 weeks
Secondary outcomes:
measure: 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
timeFrame: 1 year 6 months
measure: 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.
timeFrame: 1 year 6 months
measure: Overall survival (OS) as defined as the time from CRT until death from any cause.
timeFrame: 1 year 6 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Huntsman Cancer Institute/ University of Utah
name: Matthew Gumbleton, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: