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Recurrent Glioblastoma MultiformePhase 4NCT01756729

Post-approval Study of NovoTTF-100A in Recurrent GBM Patients

A Phase 4 study testing NovoTTF-100A in people with Recurrent Glioblastoma Multiforme, run by NovoCure Ltd. at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a non-randomized, concurrent control study, designed to confirm that the efficacy of the NovoTTF-100A System in patients with recurrent GBM treated in a real life settings following approval is comparable to that of BSC chemotherapy patients. Read more about this study

Who is it for?
Ages 22 years and older
Conditions the study is for
Recurrent Glioblastoma Multiforme
What is being tested?
NovoTTF-100A
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
12 sitesUnited States
Study dates
Dec 2012to Jan 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 22 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 22 years of age or older
  • Histological diagnosis of GBM (WHO grade IV)
  • Tumor located in the supra-tentorial region of the brain
  • Received maximal, safe, surgical resection
  • Received maximal radiation therapy
  • Received concomitant Temozolomide
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  • Received maintenance Temozolomide
  • First recurrence (based on radiological or histological evidence of recurrence)
  • Karnofsky performance score 70 or above
  • MMSE score 25 or above
  • Adequate amount and quality of tumor tissue from first surgical resection available for genetic profiling
  • Women of childbearing age must be on effective contraception
  • Signed informed consent
  • Stable steroid dose in past 4 weeks

Who cannot join

  • Implanted electronic medical device in the brain:
  • Deep brain stimulator
  • Vagus nerve stimulator
  • Programmable shunt
  • Skull defect without replacement
  • Unable to comply with treatment with the NovoTTF-100A device
Show all 15Show fewer
  • Pregnant
  • Prior antiangiogenic therapy (e.g., Bevacizumab/Avastin)
  • Second or subsequent recurrence
  • Any prior cytotoxic chemotherapy except Temozolomide
  • Actively participating in another therapeutic clinical trial
  • Radiological suspicion of pseudoprogression or radionecrosis
  • Radiation therapy or surgery in the past 4 weeks
  • Unable to comply with the study follow-up schedule
  • Any serious co-morbidity which is expected to affect survival more adversely than GBM

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-0111

  • University of Illinois at Chicago

    Chicago, Illinois, 60612

  • Baylor Research Institute

    Dallas, Texas, 75246

  • Geisinger Health System

    Danville, Pennsylvania, 17822

  • University of California San Diego Moores Cancer Center

    La Jolla, California, 92093

  • The Long Island Brain Tumor Center

    Lake Success, New York, 11042

  • University of Kentucky, Markey Cancer Center

    Lexington, Kentucky, 40536-0093

  • Keck Medical Center of USC

    Los Angeles, California, 90033

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Barrow Neurology Clinics

    Phoenix, Arizona, 85013

  • Washington University School of Medicine, Division of Oncology

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Prospective, Non-randomized, Concurrent Control, Open Label, Post-approval Study of NovoTTF-100A in Recurrent GBM Patient

This is a non-randomized, concurrent control study, designed to confirm that the efficacy of the NovoTTF-100A System in patients with recurrent GBM treated in a real life settings following approval is comparable to that of BSC chemotherapy patients. The device is a portable, battery operated device that was approved for the treatment of adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM), following histologically- or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Read the detailed description

PAST CLINICAL EXPERIENCE:

The effect of the electric fields generated by the NovoTTF-100A device (TTFields, TTF) has been tested in a large prospective, randomized trial, in 237 recurrent GBM patients. The outcome of subjects treated with the NovoTTF-100A device was compared to those treated with an effective best standard of care chemotherapy (including bevacizumab). NovoTTF-100A subjects had comparable overall survival to subjects receiving the best available chemotherapy in the US today. Similar results showing comparability of NovoTTF-100A to BSC chemotherapy were seen in all secondary endpoints.

Recurrent GBM patients treated with the NovoTTF-100A device in this trial experienced fewer side effects in general, significantly fewer treatment related side effects, and significantly lower gastrointestinal, hematological and infectious adverse events compared to controls. The only device-related adverse events seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality of life measures were better in NovoTTF-100A subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.

DESCRIPTION OF THE TRIAL:

Patients with GBM whose disease has first recurred despite standard treatment (Surgery, radiation therapy, Temozolomide treatment) and meet all of the requirements for participation in the study will be recruited to one of two groups based on patient preference alone:

  1. Treatment with the NovoTTF-100A device, or
  2. Treatment with the best standard of care practiced at each of the participating centers.

If recruited to the best standard of care group, patients will receive a chemotherapeutic agent chosen based on their prior treatments and the standard of care practiced at each treating center.

If recruited to the NovoTTF-100A group, the patients will be treated continuously until tumor progression. NovoTTF-100A treatment will consist of wearing four electrically insulated electrodes on the head. Electrode placement will require shaving of the scalp before treatment. Patients will continue treatment at home where they can maintain their regular daily routine.

During the trial, regardless of whether assigned to the NovoTTF-100A treatment group or the best standard of care group, patients will need to return once every month the hospital outpatient clinics where they will be examined by a physician. These routine visits will continue for as long as the patient's disease is not progressing.

During the visits to the clinic patients will be examined physically and neurologically, as well as fill in neuro-cognitive questionnaires. Adverse events data will be collected from all patients.. After this follow up plan, patients will be contacted once per month by telephone to answer basic questions about their health status.

SCIENTIFIC BACKGROUND:

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 (200 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 the building blocks of these cells to move and pile up in such a way that the cells physically explode. 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 cause these tiny motors to fall apart since they have a special type of electric charge.

As a result of these two effects, cancer tumor growth is slowed and can even reverse 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.

In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very few side effects and promising affectivity in slowing or reversing this disease.

Being tested
NovoTTF-100A
Keywords
Brain tumor, Treatment, Minimal toxicity, GBM, Glioblastoma, Recurrent, TTFields
Medical subject headings
Glioblastoma, Brain Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NovoTTF-100ADevice

    Multiple four-week courses of continuous NovoTTF-100A treatment.

Study groups in NCT01756729
Study groupRoleWhat they receive
Best Standard of CareActive comparatorPatients recruited to the BSC group will be treated according to the BSC practiced at each center.
Receives: Device: NovoTTF-100A
NovoTTF-100A (monotherapy)ExperimentalPatients will be treated continuously with the NovoTTF-100A device. NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.
Receives: Device: NovoTTF-100A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Measured: 5 years from initiation of accrual

Secondary outcomes (3)
  1. Change in neuro-cognitive function from baseline based on MMSE

    Measured: 5 years from initiation of accrual

  2. Genetic profiling of tumors and correlation with response to NovoTTF-100A treatment

    Measured: 5 years from initiation of accrual

  3. Adverse events severity and frequency

    Measured: 5 years from initiation of accrual

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Dec 2012 (estimated)
  2. Study startDec 2012
  3. Primary completionJan 2018 (estimated)
  4. Study completionJan 2018 (estimated)

Why it stopped: Amendment of Study Protocol

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01756729
Sponsor's protocol ID
EF-19
Status last verified
Feb 2016
First submitted
20 Dec 2012
Last updated
2 Mar 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.

    PubMed 15126372
  • Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.

    PubMed 17551011
  • Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.

    PubMed 22608262
  • Zhu JJ, Goldlust SA, Kleinberg LR, Honnorat J, Oberheim Bush NA, Ram Z. Tumor Treating Fields (TTFields) therapy vs physicians' choice standard-of-care treatment in patients with recurrent glioblastoma: a post-approval registry study (EF-19). Discov Oncol. 2022 Oct 14;13(1):105. doi: 10.1007/s12672-022-00555-5.

    PubMed 36239858

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing NovoTTF-100A in people with Recurrent Glioblastoma Multiforme, run by NovoCure Ltd. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Amendment of Study Protocol). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 5 years from initiation of accrual). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01756729, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2016.

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