Clinical trial NCT04689087: A Prospective, Open-label, Single-arm Clinical Study
Official title: A Prospective, Open-label, Single-arm Clinical Study Evaluating Tumor Treating Fields (TTFields) in Combination With Chemotherapy for Recurrent Glioblastom
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Recurrent Glioblastoma Multiforme
Keywords: recurrent GBM,
TTFields（Tumor Treating Fields）
chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-12-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: the study is a prospective, single-arm, open-label trial, designed to explore the efficacy and safety of Tumor-Treating Fields (TTFields) combined with second-line chemotherapy treatment in recurrent glioblastoma multiforme (GBM) , TTFields is an portable, battery operated device for chronic treatment of patients with recurrent or progressive glioblastoma multiforme (GBM) using alternating electric fields

Detailed description: PAST CLINICAL EXPERIENCE:

The effect of the electric fields generated by the TTFields has been tested in two Ⅲ phase trials in humans(EF-11\&EF-14). The data from these trials suggest TTFields may improve time to disease progression and overall survival of recurrent GBM patients. EF-11 is a randomized, controlled trial, designed to test the efficacy and safety of a new medical device.Although the number of patients in the trials is small, FDA has approved TTFields as a therapy for patients with recurrent GBM.

DESCRIPTION OF THE TRIAL:

Patients with GBM whose disease has recurred or progressed despite standard treatment (Surgery, radiation therapy, Temozolomide treatment) and meet all of the requirements for participation in the study will be included.Before receiving TTFields treatment, the patient can receive surgery again, and TTFields+BPC chemotherapy can be used after surgery; TTFields+BPC chemotherapy can also be used directly without surgery.

During the trial, TTFields treatment is a cycle (treatment course) every four weeks, and patients are required to complete at least one cycle of treatment. Recommended average daily wearing time ≥18 hours, patients will need to return once every month the hospital outpatient clinics where they will be examined by a physician and undergo routine laboratory examinations. These routine visits will continue for as long as the patient's disease is not progressing. After progression, if such occurs, patients will need to return once per month for two more months to the outpatient clinic for similar follow up examinations.

During the visits to the clinic patients will be examined physically and neurologically. A routine MRI of the head will be performed at baseline and after 2, 4 and 6 months. After this follow up plan, patients will be contacted once per month by telephone to answer basic questions about their health status. If the disease progresses, imaging tumor assessment or survival follow-up will be performed every 2 months thereafter, until 12 months of follow-up.

The investigator will use the RANO evaluation criteria for tumor imaging assessment, and classify the objective tumor response as follows: The objective tumor response status based on the evaluation of the target lesion can be: complete response (CR), partial response (PR), stable disease ( SD), disease progression (PD).

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 (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.

Eligibility criteria: Inclusion Criteria:

1. Sign written informed consent prior to any procedure related to the study;
2. Recurrence and pathologically confirmed WHO Grade IV glioblastoma (GBM);
3. The tumor is located in the supratentorial area
4. Age ≥18 years;
5. Received radiotherapy and maintenance treatment with temozolomide;
6. Expected survival time: \> 3 months;
7. KPS score ≥60;
8. Ability to comply with the plan;

Exclusion Criteria:

1. Other clinical trials are being tried
2. Had major surgery within 4 weeks before the start of the study or had not recovered after the surgery
3. Received radiotherapy within 4 weeks before the study
4. Received chemotherapy within 4 weeks before the study
5. Women during pregnancy;
6. Allergic to hydrogels;
7. There are important implants in the body, such as pacemaker, defibrillator, shunt tube, deep brain stimulator, etc.;
8. Patients with significantly increased intracranial pressure (shifted \>5mm in imaging midline, obvious papilloma, nausea, vomiting, and decreased consciousness)

Primary outcomes:
measure: OS6
timeFrame: 6 months
Secondary outcomes:
measure: Overall survival at 12 months (OS12)
timeFrame: 12 months
measure: overall survival OS(refers to the time from enrollment to tumor disease death from various causes)
timeFrame: 2 years
measure: Progression-free survival PFS
timeFrame: 2 years
measure: security
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yonggao Mu
role: STUDY_CHAIR
References: