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Improving Tumor Treating Fields Treatment for Brain Cancer Patients With Skullremodeling Surgery (Neurosurgery) (OptimalTTF-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04223999
Recruitment Status : Not yet recruiting
First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborators:
NovoCure GmbH
Odense University Hospital
Information provided by (Responsible Party):
Anders Rosendal Korshøj, Aarhus University Hospital

Brief Summary:

The aim of this trial is to test a new potential treatment, skullremodeling surgery (SR-surgery) combined with tumor treating fields (TTFields), for patients with first recurrence of malignant brain tumor (first recurrence of glioblastoma). Glioblastoma is one of the most malignant cancers.

TTFields is a new treatment for brain cancer (glioblastoma), which is used in additional to surgery (removal of the tumor), chemotherapy and radiation. TTFields work by sending alternating current to the tumor. The current disrupts cell division and thus prevents cancer growths. Electrodes are placed on the scalp and the current is delivered via a small portable battery (1kg). Treatment duration is 18 hours during the day, where the patient can do normal daily activities. The average life expectancy of a newly diagnosed brain cancer patient (glioblastoma) is increased from 15 months to 21 months by adding TTFields.

SR-surgery is a minor and safe procedure, that involves creating small burrholes in the skull over the tumor location. The burrholes are approximately 15 mm in diameter. The burrholes increase the electric current in the tumor by funneling the electricity trough the path of least resistance, since bone hinders the electricity.

The theory is that combining TTFields with SR-surgery we can increase the effect of TTFields and in return increase overall survival for brain cancer patients.

The investigators have recently finished a phase 1 clinical trial, with 15 trial participants, testing the safety and efficacy of our combined treatment. The investigators concluded that TTFields and SR-surgery combined is safe and showed promising results by increasing overall survival with the trial participants.

Therefor we wish to proceed with a phase 2 trial.

Method The investigators aim to include 70 patients with first recurrence of glioblastoma (brain cancer). Each patient will be randomized to one of two treatment arms. Both treatment arms will receive the best current brain tumor treatment. In addition, one arm receives TTF and the other arm TTFields and SR-surgery.

All patients are expected to receive better treatment than current best practice, since TTFields is not standard treatment in Denmark.

The primary aim of the trial is to assess the 12-month overall survival in both groups. The theory is that more trial participants will be alive after 12 months in the group that receives both TTF and SR-surgery.

The trial duration is 36 months with an average expected follow-up of 18 months.


Condition or disease Intervention/treatment Phase
Recurrent Glioblastoma Procedure: Skullremodeling surgery Other: Control Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized 1:1 to one of two study arms to receive either, 1) skullremodeling-surgery, TTFields and best practice medical oncological therapy (interventional arm), or 2) TTFields and best practice medical oncological therapy alone (control arm).
Masking: Single (Outcomes Assessor)
Masking Description:

Skullremodeling surgery prevents the participant, careprovider and investigator to be blinded to the randomization.

The outcome assessors (statisticians) will be blinded when analysing the data.

Primary Purpose: Treatment
Official Title: Enhancing Tumor Treating Fields for Recurrent Glioblastoma With Targeted and Individualised Skullremodeling Surgery: A Multi-center Randomized Phase 2 Trial
Estimated Study Start Date : March 1, 2020
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
In this arm, trial participants receive the intervention that is being tested, skullremodeling surgery. This is in combination with tumor treating fields and best practice medical treatment.
Procedure: Skullremodeling surgery
Strategically placed cranial burrholes in order to improve the TTField "dose" focally in the tumor.
Other Name: SR-surgery

Active Comparator: Control

In this arm, the trial participant receives tumor treating fields and best practice medical treatment.

This serves as an active comparative control arm to the intervention.

Other: Control
Tumor treating fields combined with best medical treatment.




Primary Outcome Measures :
  1. OS12 [ Time Frame: 12 months from the time of randomization. ]
    12-month overall survival.


Secondary Outcome Measures :
  1. Median OS [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 month. ]
    Median overall survival.

  2. Median PFS [ Time Frame: From date of randomization until the date of first documented progression, assessed up to 36 months. ]
    Median progression-free survival.

  3. OS24 [ Time Frame: 24 months from the time of randomization. ]
    24-month overall survival

  4. OS36 [ Time Frame: 36 months from the time of randomization. ]
    36-month overall survival

  5. PFS6 [ Time Frame: 6 months from the time of randomization ]
    6-month progression-free survival

  6. ORR [ Time Frame: Assessed every 3. month, up to 36 months or death, whichever comes first. ]
    Overall objective response rate assessed by modified RANO criteria

  7. Standardised and verified quality of life assessment questionnaires (QLQ-C30 and QLQ-BN20) for cancer and brain tumor patients. [ Time Frame: Assessed at inclusion and every 3. month, assessed up to 36 months or death, whichever comes first. ]
    Standardised and verified questions related to quality of life to cancer and brain tumor patients. Quality of life is rated by the patients own thoughts about the current situation and future and also the presence or absence of the most common symptoms in cancer and brain tumors. Rated from a scale 1-4 (none to a lot) and 1-7 scale (very poor to very good).

  8. Steroid dose [ Time Frame: From the time of inclusion and every 3. month, assessed up to 36 months or death, whichever comes first. ]
    Cumulative corticosteroid usage

  9. KPS [ Time Frame: From time of inclusion and every 3. month, assessed up to 36 months or death, whichever comes first. ]
    Assessing KPS.

  10. AE [ Time Frame: From time of inclusion and every 3. month, assessed up to 36 months or death, whichever comes first. ]
    Adverse events / Safety. All adverse events observed by personnel or reported by trial participant.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age 18 years or older
  2. progressive GBM based on the RANO criteria and whole brain MRI according to the consensus recommendations for a standardized brain tumor imaging protocol in clinical trials , not older than 4 weeks from the assessment
  3. estimated survival≥ 3 months
  4. supratentorial tumor location
  5. focal disease in the vicinity of the previously known tumor or resection cavity,
  6. KPS≥70
  7. ability to comply with TTFields treatment
  8. eligibility for diagnostic or therapeutic neurosurgery and subsequent best practice oncological therapy,
  9. tumor characteristics indicating significant expected benefit from feasible craniectomy or SR-surgery combined with TTFields i.e. (a) focal tumor and (b) most superficial border of tumor or resection cavity closer than 2 cm from brain surface
  10. use of validated anticonception for fertile female participants in concordance with guidelines provided by the danish health and medicines authority,
  11. signed written consent form

Exclusion Criteria:

  1. pregnancy or nursing (fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy)
  2. infra-tentorial tumor
  3. implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmia
  4. uncontrollable symptomatic epilepsy refractory to standard medication
  5. contraindications for skullremodeling surgery, e.g.bleeding diathesis or severe infection
  6. significant co-morbidities, i.e. (a)significant liver function impairment (alt >210 u/l for men and > 135 u/l for women or total bilirubin >25umol/l), (b)significant renal impairment (serum creatinine > 1.7 mg/dl= 150 umol/l), (c)coagulopathy (inr> 1.8 or aptt > 57s), (d) thrombocytopenia (platelet count < 100 x 103/μl =100 x 109/l), (e) neutropenia (anc< 1.5 x 103/μl =1.5 x 109/l), (f) anemia ( hb < 10 g/l= 6.0 mmol/l)
  7. severe cognitive impairment
  8. active participation in another therapeutic interventional clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04223999


Contacts
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Contact: Nikola Mikic, MD +4593972105 nikolanm@gmail.com
Contact: Anders R Korshøj, MD, PhD +4523882226 andekors@gmail.com

Locations
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Denmark
Aarhus University Hospital
Aarhus, Denmark, 8200
Sponsors and Collaborators
Anders Rosendal Korshøj
NovoCure GmbH
Odense University Hospital
Investigators
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Principal Investigator: Anders R Korshøj, MD, PhD Aarhus University Hospital

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Responsible Party: Anders Rosendal Korshøj, Principal Investigator, Associate Professor, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT04223999    
Other Study ID Numbers: 150919V1
68928/1-10-72-214-19 ( Other Identifier: The Danish Central Region Committee on Health Research Ethics )
658876/1-16-02-277-19 ( Other Identifier: The Danish Data Protection Agency )
2019081231 ( Other Identifier: The Danish Medical Agency )
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All data published will be available upon request. Study protocol will be published.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anders Rosendal Korshøj, Aarhus University Hospital:
Enhancing tumor treating fields
Optimizing tumor treating fields
tumor treating fields
Brain cancer
Recurrent glioblastoma
Glioblastoma
Glioblastom
TTFields
Clinical trial
Phase 2
Skullremodeling surgery
Skull remodeling surgery
SR-surgery
Experimental neurosurgery
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue