To test the efficacy and safety of TTFields, using the NovoTTF-200T System, concurrent with standard therapies for stage 4 NSCLC patients, followingprogression while on or after platinum based treatment
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall Survival (OS) of patients treated with TTFields + docetaxel or immune
checkpoint inhibitors Vs. docetaxel or immune checkpoint inhibitors alone
(Superiority analysis)
Secondary outcome
Key secondary endpoints:
- Overall Survival of patients treated with TTFields + Docetaxel Vs. Docetaxel
alone (Superiority analysis)
- Overall Survival of patients treated with TTFields + Immune checkpoint
inhibitors Vs. immune checkpoint inhibitors alone (Superiority analysis)
Additional secondary endpoints:
- Overall Survival of patients treated with TTFields + Docetaxel Vs. immune
checkpoint inhibitors alone (non-inferiority analysis)
- Progression-free survival of patients treated with Docetaxel or Immune
checkpoint inhibitors + TTFields vs. Docetaxel or Immune checkpoint
inhibitors alone, based on RECIST criteria
- Overall radiological response rate (based on RECIST criteria) of patients
treated with Docetaxel or Immune checkpoint inhibitors + TTFields vs.
Docetaxel or Immune checkpoint inhibitors alone.
- Quality of life of patients treated with docetaxel or Immune checkpoint
inhibitors concomitant with TTFields compared to that of patients who are
treated with docetaxel or Immune checkpoint inhibitors without TTFields, using
the EORTC QLQ C30 questionnaire with LC13 addendum.
- Analyses of the effects of NovoTTF-200T with each type of immune checkpoint
inhibitor on OS and PFS
- Analysis of the effects of NovoTTF-200T on OS and PFS within each
histological subgroup (squamous and non-squamous)
- The effect of treatment usage time with NovoTTF-200T (as calculated from the
device log file) to check whether average monthly usage time of
over 75% of the time leads to better OS and PFS outcomes, as seen in
glioblastoma patients treated with TTFields
- Adverse events, severity and frequency, in patients treated with docetaxel or
Immune checkpoint inhibitors concomitant with TTFields using the NovoTTF-200T
System compared to patients treated with docetaxel or Immune checkpoint
inhibitors alone
Background summary
In a single arm pilot study (phase I/II), 42 inoperable stage IIIB (with
pleural effusion) and IV NSCLC patients who had had tumor progression after at
least one line of prior chemotherapy received pemetrexed 500mg/m2 intravenously
every 3 weeks together with continuous daily 150 kHz TTFields (for 12 hours per
day) applied to the chest and upper abdomen until disease progression. The
primary endpoint was time to "in-field" progression. Median age was 63 years,
76 % had stage IV disease, 78% had adenocarcinoma and 17% had an Eastern
Cooperative Oncology Group (ECOG) performance status of 2.
The median time to in-field progression was 28 weeks and the median time to
progression was 22 weeks. Six patients (14.6 %) had a partial response (PR) and
20 (48.8%) had stable disease (SD). The median overall survival was 13.8 months
(compared to the historical control of 8.3 months reported in the phase III
trial of pemetrexed alone compared to docetaxel) and the 1 year survival rate
was 57% (compared to the historical control of 30% reported for pemetrexed
alone). Given that it is now known that pemetrexed has no benefit for squamous
histology, it is interesting to note that in an exploratory analysis of
histology subsets, patients with tumors of adenocarcinoma histology had an
overall survival of 12.8 months (n=35) and patients with tumors of squamous
cell histology had an overall survival of 13.8 months (n=7). The combination
was well tolerated and, compared to a pemetrexed historical control, there was
no increase in the adverse event rate, GI toxicity or hepatic toxicity and no
device related cardiac arrhythmias were reported. There were also no
TTFields-related serious adverse events. The only device-related adverse event
was mild to moderate contact dermatitis in 14 patients, which was expected with
use of the transducer arrays. Therapy usage time was very good with 85% of
patients adhering to the recommended TTFields schedule.
The hypothesis of this study is that the use of TTFields concurrent to standard
of care therapies in stage 4 NSCLC after platinum failure will increase overall
survival compared to patients receiving standard therapies alone.
Study objective
To test the efficacy and safety of TTFields, using the NovoTTF-200T System,
concurrent with standard therapies for stage 4 NSCLC patients, following
progression while on or after platinum based treatment
Study design
Pivotal, randomized, open-label study of Tumor Treating Fields (TTFields)
concurrent with standard of care therapies for treatment of stage 4 non-small
cell lung cancer (NSCLC) following platinum failure
Intervention
Each patient has 50% chance of being enrolled into one of the following two
groups:
• The TTFields group: Patients receive chemotherapy or immunotherapy with
TTFields
-OR-
• The control group: Patients only receive chemotherapy or immunotherapy
Your study doctor will choose between the standard care consisting of docetaxel
chemotherapy or immunotherapy with a PD- L1/PD-1 inhibitor (Atezolizumab,
Nivolumab of Pembrolizumab) according to the best practices of the institution
with appropriate premedication. These medicines are approved for the treatment
of your disease and are administered at their standard dose at standard
frequency.
Chemotherapy or immunotherapy is administered intravenously (injection in the
vein) at the hospital or the clinic. Your doctor may prescribe other
medications for or after your chemotherapy to prevent side effects. Your doctor
will decide how long you will be treated with chemotherapy or immunotherapy.
Study burden and risks
TTFields:
The treatment with the NovoTTF-200T may cause localized skin irritation, skin
breakdown or infection at the sites where the electrodes are in contact with
skin; if this happens, the patient will be evaluated and treated by the doctor
and he/she should heal completely after the treatment has been stopped.
Additionally, the treatment with TTFields may not delay tumor progression or
cause regression.
Other potential risks of an electric device, such as the Novo TTF-200T, are the
risk of electric or mechanical faults, electric shocks and electromagnetic
interference (generating electromagnetic fields that may influence other
components within the device or other devices). However, Novocure has taken
appropriate precautions to limit the chance of these risks.
The device is safe and very unlikely to form a risk to others. It should not
interfere with the operation of other normal electronic devices.
Other currently unknown risks and discomforts may occur. This is why it is very
important that any new health problems are reported to the investigator as soon
as possible.
The possible risks and discomforts of chemotherapy, immunotherapy and the
assessments are available in Appendix D of the ICF.
Park 6
Root D4 CH-6039
CH
Park 6
Root D4 CH-6039
CH
Listed location countries
Age
Inclusion criteria
1. 18 years of age and older
2. Life expectancy of >= 3 months
3. Histological or cytological diagnosis of squamous or non-squamous,
inoperable, metastatic NSCLC.
4. Diagnosis of radiological progression while on or after first platinum-based
systemic therapy administered for advanced or metastatic disease
a. Patients who received adjuvant or neoadjuvant platinum-based chemotherapy
(after surgery and/or radiation therapy) and developed metastatic disease
within 6 months of completing therapy are eligible.
b. Patients with metastatic disease more than 6 months after adjuvant or
neoadjuvant platinum-based chemotherapy, who also subsequently progressed
during or after a platinum- based regimen given to treat the advanced or
metastatic disease, are eligible.
c. Patients should not receive any systemic therapy after platinum failure
before enrollment into the study. Maintenance therapy after platinum based
therapy and prior to progression is allowed.
5. ECOG Score of 0-2
6. Assigned by the physician to receive either docetaxel or immune checkpoint
inhibitor per standard of care regimens
7. Able to operate the NovoTTF-200T device independently or with the help of a
caregiver
8. Signed informed consent for the study protocol
Exclusion criteria
1. Metastases to central nervous system (CNS) with clinical symptoms or
evidence of new metastases to CNS during screening. Patients who previously
received treatments for the metastases to CNS, are stable and meet the
following requirements are allowed to be enrolled:
a. The patients are neurologically returned to baseline (except for residual
signs or symptoms related to CNS treatment).
b. No treatment for the metastases to CNS during the screening period (e.g.
surgery, radiotherapy, corticosteroid therapy- prednisone > 10 mg/day or
equivalent).
c. No progress in CNS lesions as indicated by MRI within 14 days prior to
randomization.
d. No meningeal metastasis or spinal cord compression.
2. Patients planned to receive immune checkpoint inhibitor with contra-
indications to receive immunotherapy
3. Patients planned to receive docetaxel with contra- indications to receive
docetaxel
4. Severe comorbidities:
- a. Clinically significant (as determined by the investigator) hematological,
hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10 9/L and
platelet count < 100 x 10 9/L; bilirubin > 1.5 x ULN; AST and/or ALT > 2.5 x
ULN or > 5 x ULN if patient has
documented liver metastases; and serum creatinine > 1.5 x ULN.
b. History of significant cardiovascular disease unless the disease is well
controlled. Significant cardiac disease includes second/third degree heart
block; significant ischemic heart disease; poorly controlled hypertension;
congestive heart failure of the New York
Heart Association (NYHA) Class II or worse (slight limitation of physical
activity; comfortable at rest, but ordinary activity results in fatigue,
palpitation or dyspnea).
c. History of arrhythmia that is symptomatic or requires treatment. Patients
with atrial fibrillation or flutter controlled by medication are not excluded
from participation in the study.
d. History of pericarditis
e. History of interstitial lung disease
f. History of cerebrovascular accident (CVA) within 6 months prior to
randomization or that is not stable.
g. Active infection or serious underlying medical condition that would impair
the ability of the patient to receive protocol therapy.
h.History of any psychiatric condition that might impair patient's ability to
understand or comply with the requirements of the study or to provide consent.
i. Any other malignancy requiring anti-tumor treatment in the past three years,
excluding treated stage I prostate cancer, in situ cervical cancer, in situ
breast cancer and nonmelanomatous skin cancer.
5. Concurrent treatment with other experimental treatments for NSCLC while on
the study
6. Implantable electronic medical devices (e.g. pacemaker, defibrilator) in the
upper torso
7. Known allergies to medical adhesives or hydrogel
8. Pregnancy or breast-feeding (patients with reproductive potential must use
effective contraception methods throughout the entire study period, as
determined by their investigator/gynecologist)
9. Admitted to an institution by administrative or court order
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02973789 |
| CCMO | NL61747.078.17 |