Trial Title:
Tumor Treating Fields for Locally Advanced NSCLC
NCT ID:
NCT06124118
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Durvalumab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Bayes optimal interval design (BOIN)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
carboplatin chemotherapy
Description:
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.
Arm group label:
Device Duration Level 2
Other name:
paclitaxel
Other name:
nab-paclitaxel
Intervention type:
Device
Intervention name:
NovoTTF-200T (TTFields) System
Description:
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.
Arm group label:
Device Duration Level 1
Arm group label:
Device Duration Level 2
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
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.
Arm group label:
Device Duration Level 1
Arm group label:
Device Duration Level 2
Other name:
Imfinzi
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.
Criteria for 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.
Gender:
All
Minimum age:
22 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kaitlin Stephens
Phone:
801-213-8494
Email:
Kaitlin.Stephens@hci.utah.edu
Start date:
April 4, 2024
Completion date:
November 15, 2026
Lead sponsor:
Agency:
University of Utah
Agency class:
Other
Source:
University of Utah
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06124118
