A Prospective, Non-randomized, Concurrent Control, Open Label, Post-approval Study of NovoTTF-100A in Recurrent GBM Patient
Description
Brief 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. 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.
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.
Phase
N/AInclusion and Exclusion Criteria
- 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
- 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
- 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
- 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
Sites
-
California
- Keck Medical Center of USC, Los Angeles, California, 90033
- University of California San Diego Moores Cancer Center, La Jolla, California, 92093
-
Arizona
- Barrow Neurology Clinics, Phoenix, Arizona, 85013
-
Missouri
- Washington University School of Medicine, Division of Oncology, St. Louis, Missouri, 63110
-
Illinois
- University of Illinois at Chicago, Chicago, Illinois, 60612
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