A Prospective, Open-label, Single-arm Clinical Study

A Prospective, Open-label, Single-arm Clinical Study Evaluating Tumor Treating Fields (TTFields) in Combination With Chemotherapy for Recurrent Glioblastom

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

Study Overview

• Status: Unknown
• Conditions: Recurrent Glioblastoma Multiforme
• Intervention / Treatment: Combination product: TTFields

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qunying Yang; Phone Number: 13802971439; Email: Yangqy@sysucc.org.cn
• Study Contact Backup: Name: Yonggao Mu, Chief; Phone Number: 13808816691; Email: Mouyg@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Yonggao Mu, Chief; Phone Number: 13808816691; Email: Mouyg@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Second line conventional treatment	Combination product: TTFields; For patients with relapsed GBM, before receiving electric field treatment, the patient can be re-operated, and TTFields+BPC chemotherapy is used after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS6	Overall survival at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival at 12 months (OS12)	To evaluate the OS12 of patients with recurrent glioblastoma treated with TTFields combined with chemotherapy	12 months
overall survival OS(refers to the time from enrollment to tumor disease death from various causes)	To evaluate the OS of patients with recurrent glioblastoma treated with tumor electric field therapy combined with chemotherapy	2 years
Progression-free survival PFS	To evaluate the PFS of patients with recurrent glioblastoma treated with tumor electric field therapy combined with chemotherapy according to RANO standard	2 years
security	Adverse events and severe adverse events occurred during treatment were recorded by CTCAE V5.0, and the safety of tumor electric field therapy combined with chemotherapy was analyzed	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Yonggao Mu, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 25, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): December 30, 2020
• Last Update Submitted That Met QC Criteria: December 25, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: chemotherapy; recurrent GBM,; TTFields（Tumor Treating Fields）
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: M-TTFields

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No