NCT05698264

Brief Summary

Low intensity, intermediate frequency (100-300 kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields) were found to have a profound inhibitory effect on the growth rate of a variety of human cancer cells. Previous study showed anti-tumor activity in respect of melanoma, glioblastoma (GBM), breast carcinoma and NSCLC cell lines. This study aims to assess the impact of TTFields on NSCLC though the understanding of tumor evolution and peripheral lymphocytes activity and proliferation. Concomitant to drug therapy, patients will receive treatment with Tumor Treating Fields (TTFields), generated by the medical device NovoTTF-200T with a recommended duration of minimum 18 h a day. TTFields administered using insulated transducer arrays applied to the skin surrounding the region of a malignant tumor. 50 patients will be recruited according to the study design in two cohorts and will receive TTFields therapy: Cohort A: Adult NSCLC EGFR positive mutation. Cohort B: Adult NSCLC patients to be treated with PD-1 inhibitors. The cohort A will focus on the clonal evolution in EGFR mutated lung cancer patients by using circulating tumor DNA (ctDNA) analysis of paired baseline and end-of-treatment (EOT) plasma samples. The cohort B will study the impact of TTField on the profile, activity, and proliferation of peripheral lymphocytes. Lymphocytes will be purified from whole blood samples for the profile, proliferation, and activity analyzed by FACS. Treatment with TTFields will be administered until progressive disease, unacceptable toxicity1, withdrawal of consent or death. After the end of treatment, the patients will be followed until data cutoff date or 2 years after the last patient had entered the study.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
31mo left

Started Jan 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress57%
Jan 2023Dec 2028

First Submitted

Initial submission to the registry

November 23, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

January 20, 2023

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 26, 2023

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

January 26, 2023

Status Verified

January 1, 2023

Enrollment Period

4.9 years

First QC Date

November 23, 2022

Last Update Submit

January 22, 2023

Conditions

Non Small Cell Lung CancerEGFR Gene MutationImmune Checkpoint Inhibitor

Keywords

TTFieldsimmune checkpoint inhibitorNon Small Cell Lung CancerNSCLCEGFR Gene Mutation

Outcome Measures

Primary Outcomes (3)

  • Molecular ctDNA characterization under concomitant TTFields therapy - cohort A (EGFR)

    The primary outcome measure will be the rate of new somatic mutation detection in circulating tumor DNA (ctDNA) using Next Generation Sequencing (NGS) in patients receiving concurrent TTFields therapy. The measure will be reported as the percentage of patients showing new somatic mutations upon progression of their disease following TTFields treatment.

    5 years

  • In vitro peripheral lymphocytes activity characterization under concomitant TTFields therapy - cohort B (under PD-1 inhibitors treatment)

    The primary outcome measure will be the evaluation of the impact of combining PD-1 inhibitors with TTFields therapy on peripheral lymphocyte activity using an in vitro assay. Whole blood samples will be collected and the assay will involve the isolation, activation, and labeling of peripheral lymphocytes from patients in cohort B with a panel of antibodies. The analysis will be performed using flow cytometry (FACS) and the longitudinal changes in peripheral lymphocyte activity will be correlated with each patient's response.

    5 years

  • Characterization of the impact of TTFields on peripheral lymphocytes proliferation ex-vivo - cohort B (PD-1 inhibitors treatment)

    The primary outcome measure will be the quantification of peripheral lymphocyte proliferation in patients receiving PD-1 inhibitors therapy using an in vitro assay. Whole blood samples will be collected and the assay will involve the isolation, labeling, and analysis of peripheral lymphocytes with carboxyfluorescein diacetate succinimidyl ester (CFSE). Proliferation will be measured using flow cytometry (FACS) and the longitudinal changes in peripheral lymphocyte proliferation will be correlated with each patient's response to the therapy in cohort B.

    5 years

Secondary Outcomes (3)

  • Safety will be assessed by recording adverse events in both cohorts.

    5 years

  • Objective response rate

    5 years

  • DoR

    5 years

Study Arms (2)

NSCLC patients with EGFR mutation

EXPERIMENTAL

The cohort A will focus on the clonal evolution in EGFR mutated lung cancer patients by using circulating tumor DNA (ctDNA) analysis of paired baseline and end-of-treatment (EOT) plasma samples. This cohort will be compared to matched EGFR patients previously analyzed by our group. Analysis of paired samples from this study will allow a dissection of events acquired through therapy, specifically which component of the combination therapy may be driving selection of the mutations in comparison with the control group without TTFields.

Device: concomitant TTFields treatment device to standard of care EGFR positive NSCLC treatment

NSCLC patients planned to receive PD-1 inhibitors

EXPERIMENTAL

The cohort B will study the impact of TTField on the profile, activity, and proliferation of peripheral lymphocytes in NSCLC patients receiving PD-1 inhibitors concomitant to TTFields treatment. Lymphocytes will be purified from whole blood samples for the profile, proliferation, and activity analyzed by FACS.

Device: concomitant TTFields treatment device to standard of care anti PD-1 NSCLC treatment

Interventions

concomitant TTFields treatment device to standard of care EGFR positive NSCLC treatmentDEVICE

Concomitant to drug therapy, patients will receive treatment with Tumor Treating Fields (TTFields), generated by the medical device NovoTTF-200T with a recommended duration of minimum 18 h a day. TTFields administered using insulated transducer arrays applied to the skin surrounding the region of a malignant tumor.

NSCLC patients with EGFR mutation
concomitant TTFields treatment device to standard of care anti PD-1 NSCLC treatmentDEVICE

Concomitant to drug therapy, patients will receive treatment with Tumor Treating Fields (TTFields), generated by the medical device NovoTTF-200T with a recommended duration of minimum 18 h a day. TTFields administered using insulated transducer arrays applied to the skin surrounding the region of a malignant tumor.

NSCLC patients planned to receive PD-1 inhibitors

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male and female patients 18 years of age and older.
  • Have histologically or cytologically confirmed lung cancer.
  • Documented next generation sequencing assay performed on tumor sample in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.
  • Have at least 1 measurable lesion per RECIST v1.1
  • Have life expectancy ≥3 months.
  • Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • Must provide a signed and dated informed consent indicating that the participants have been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
  • Have the willingness and ability to comply with scheduled visits and study procedures.
  • Cohort A, confirmed EGFR mutation.

You may not qualify if:

  • Implanted electronic devices (e.g. pacemaker) in the upper torso.
  • Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ or prostate cancer, which are allowed within 3 years).
  • Have any condition or illness that, in the opinion of the investigator, would compromise participants' safety or interfere with the evaluation.
  • Be pregnant or breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Shaare Zedek Medical Center

Jerusalem, Israel

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Central Study Contacts

Nir Peled, MD

CONTACT

+972587040620nirp@szmc.org.il

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Head of Oncology

Study Record Dates

First Submitted

November 23, 2022

First Posted

January 26, 2023

Study Start

January 20, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Last Updated

January 26, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

IL(1)