Clinical Trials /

Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure (LUNAR)

NCT02973789

Description:

The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-100L System, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum based treatment.The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure (LUNAR)
  • Official Title: LUNAR: 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

Clinical Trial IDs

  • ORG STUDY ID: EF-24
  • NCT ID: NCT02973789

Conditions

  • Nonsmall Cell Lung Cancer

Interventions

DrugSynonymsArms
Immune checkpoint inhibitors or docetaxelBest Standard of Care

Purpose

The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-100L System, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum based treatment.The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Detailed Description

      PAST PRE-CLINICAL AND CLINICAL EXPERIENCE:

      The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in
      vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in
      combination with chemotherapies and PD-1 inhibitors. TTFields have been demonstrated to act
      synergistically with taxanes and have been shown to be additive when combined with PD-1
      inhibitors. In addition, TTFields have shown to inhibit metastatic spread of malignant
      melanoma in in vivo experiment.

      In a pilot study, 42 patients with advanced NSCLC who had had tumor progression after at
      least one line of prior chemotherapy, received pemetrexed together with TTFields (150 kHz)
      applied to the chest and upper abdomen until disease progression (Pless M., et al., Lung
      Cancer 2011). The combination was well tolerated and the only device-related adverse event
      was mild to moderate contact dermatitis. Efficacy endpoints were remarkably high compared to
      historical data for pemetrexed alone.

      In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active
      chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active
      chemotherapy in extending survival, associated with minimal toxicity, good quality of life,
      and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a
      phase III trial of Optune® combined with maintenance temozolomide compared to maintenance
      temozolomide alone has shown that combined therapy led to a significant improvement in both
      progression free survival and overall survival in patients with newly diagnosed glioblastoma
      without the addition of high grade toxicity and without decline in quality of life (Stupp R.,
      et al., JAMA 2015).

      DESCRIPTION OF THE TRIAL:

      All patients included in this trial are patients with squamous or non-squamous, stage 4 NSCLC
      who had disease progression on or after receiving platinum based chemotherapy. In addition,
      all patients must meet all eligibility criteria.

      Eligible patients will be randomly assigned to one of two groups:

      Patients receive docetaxel or immune checkpoint inhibitor in combination with TTFields using
      the NovoTTF-100L System.

      Patients receive docetaxel or immune checkpoint inhibitor without TTFields. Patients will be
      randomized at a 1:1 ratio. Baseline tests will be performed in patients enrolled in both
      arms. If assigned to the NovoTTF-100L group, the patients will be treated continuously with
      the device until disease progression in the thorax and/or liver according to RECIST or
      irRECIST (Immune-Related Response Evaluation Criteria In Solid Tumors) (depending if the
      patient is receiving docetaxel or immune checkpoint inhibitor, respectively).

      On both arms, patients who have disease progression according to RECIST or irRECIST
      (depending if the patient is receiving docetaxel or immune checkpoint inhibitor,
      respectively) will switch to a third line treatment according to local practice.

      SCIENTIFIC BACKGROUND:

      Electric fields exert forces on electric charges similar to the way a magnet exerts forces on
      metallic particles within a magnetic field. These forces cause movement and rotation of
      electrically charged biological building blocks, much like the alignment of metallic
      particles seen along the lines of force radiating outwards from a magnet.

      Electric fields can also cause muscles to twitch and if strong enough may heat tissues.
      TTFields are alternating electric fields of low intensity. This means that they change their
      direction repetitively many times a second. Since they change direction very rapidly (150
      thousand times a second), they do not cause muscles to twitch, nor do they have any effects
      on other electrically activated tissues in the body (brain, nerves and heart). Since the
      intensities of TTFields in the body are very low, they do not cause heating.

      The breakthrough finding made by Novocure was that finely tuned alternating fields of very
      low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in
      the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are
      multiplying, TTFields cause electrically-charged cellular components of these cells to change
      their location within the dividing cell, disrupting their normal function and ultimately
      leading to cell death. In addition, cancer cells also contain miniature building blocks which
      act as tiny motors in moving essential parts of the cells from place to place. TTFields
      interfere with the normal orientation of these tiny motors related to other cellular
      components since they are electrically-charged as well. As a result of these two effects,
      tumor cell division is slowed, results in cellular death or reverses after continuous
      exposure to TTFields.

      Other cells in the body (normal healthy tissues) are affected much less than cancer cells
      since they multiply at a much slower rate if at all. In addition TTFields can be directed to
      a certain part of the body, leaving sensitive areas out of their reach. Finally, the
      frequency of TTFields applied to each type of cancer is specific and may not damage normally
      dividing cells in healthy tissues.

      In conclusion, TTFields hold the promise of serving as a brand new treatment for NSCLC with
      very few side effects.
    

Trial Arms

NameTypeDescriptionInterventions
NovoTTF-100LExperimentalPatients receive TTFields using the NovoTTF-100L System together with immune checkpoint inhibitors or docetaxel
  • Immune checkpoint inhibitors or docetaxel
Best Standard of CareActive ComparatorPatients receive best standard of care with immune checkpoint inhibitors or docetaxel
  • Immune checkpoint inhibitors or docetaxel

Eligibility Criteria

        Inclusion Criteria:

          1. 22 years of age and older

          2. Life expectancy of ≥ 3 months

          3. Histological diagnosis of squamous or non-squamous, inoperable, stage 4 NSCLC

          4. Diagnosis of radiological progression while on or after first platinum-based systemic
             therapy

          5. Randomization within 28 days of diagnosis of last progression

          6. ECOG Score of 0-2

          7. Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor
             per standard of care regimens

          8. Able to operate the NovoTTF-100L device independently or with the help of a caregiver

          9. Signed informed consent for the study protocol

        Exclusion Criteria:

          1. Presence of brain metastasis or leptomeningeal spread of the disease

          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:

               1. 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

               2. 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)

               3. 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 trial

               4. History of pericarditis

               5. History of interstitial lung disease

               6. History of cerebrovascular accident (CVA) within 6 months prior to randomization
                  or that is not stable

               7. Active infection or serious underlying medical condition that would impair the
                  ability of the patient to received protocol therapy

               8. 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

               9. 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 non-melanomatous skin cancer

          5. Concurrent treatment with other experimental treatments for NSCLC while on the study

          6. Implantable electronic medical devices (e.g. pacemaker, defibrillator) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:22 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival of patients treated with TTFields + docetaxel or immune checkpoint inhibitors vs. docetaxel or immune checkpoint inhibitors alone (superiority analysis)
Time Frame:4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival of patients treated with TTFields + docetaxel vs. docetaxel alone (superiority analysis)
Time Frame:4 years
Safety Issue:
Description:
Measure:Overall survival of patients treated with TTFields + immune checkpoint inhibitors vs. immune checkpoint inhibitors alone (superiority)
Time Frame:4 years
Safety Issue:
Description:
Measure:Overall Survival of patients treated with TTFields + docetaxel Vs. immune checkpoint inhibitors alone (non-inferiority analysis)
Time Frame:4 years
Safety Issue:
Description:
Measure:Progression-free survival of patients treated with docetaxel or immune checkpoint inhibitors + TTFields vs. docetaxel or immune checkpoint inhibitors alone, based on RECIST Criteria
Time Frame:4 years
Safety Issue:
Description:
Measure: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.
Time Frame:4 years
Safety Issue:
Description:
Measure:Quality of life using the EORTC QLQ C30 questionnaire with LC13 addendum
Time Frame:4 years
Safety Issue:
Description:
Measure:Analyses of the effects of NovoTTF-100L with each type of immune checkpoint inhibitor on overall survival and progression free survival
Time Frame:4 years
Safety Issue:
Description:
Measure:Analysis of the effects of NovoTTF-100L on overall survival and progression free survival within each histological subgroup (squamous and non-squamous)
Time Frame:4 years
Safety Issue:
Description:
Measure:The effect of treatment compliance with NovoTTF-100L on overall survival and progression free survival outcomes
Time Frame:4 years
Safety Issue:
Description:
Measure:Adverse events, severity and frequency based on Common Terminology Criteria for Adverse Events (CTCAE) V4.03
Time Frame:4 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NovoCure Ltd.

Trial Keywords

  • Non-Small Cell Lung Cancer
  • NSCLC
  • Treatment
  • Minimal Toxicity
  • TTFields
  • TTF
  • Tumor Treating Fields
  • Novocure
  • Docetaxel
  • PD-1 inhibitor
  • PD-L1 inhibitor
  • Immune checkpoint inhibitor

Last Updated

May 27, 2020