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GlioblastomaPhase 2IORTNCT04681677

Recurrent GBM Treated With Neurosurgical Resection and IORT Using the Xoft Axxent eBx System and Bevacizumab

A Phase 2 study testing Radiation: Intra-operative Radiation Therapy - IORT and Bevacizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Xoft, Inc. at 1 site in United States.

Terminated

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

Official record
Search all trials

Trial summary

The purpose of this trial is to assess the overall survival of patients treated with the Xoft Axxent eBx System and post-radiation adjuvant Bevacizumab for single-fraction IORT following maximal neurosurgical resection of recurrent glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Recurrent Glioblastoma, GBM
What is being tested?
Radiation: Intra-operative Radiation Therapy - IORT and Bevacizumab
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
2 Nov 2021to 24 Apr 2024
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject has the ability to provide written informed consent
  • Subject has the willingness to comply with all study procedures for the duration of the study
  • Subject has histopathologically proven diagnosis of GBM or variants (gliosarcoma, giant cell glioblastoma etc.). Subjects will be also eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
  • Subjects must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced MRI within 21 days prior to enrollment
  • Subjects must have passed an interval of 6 months or greater between completion of prior radiotherapy and enrollment. If subjects have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:
  • New areas of tumor outside the original radiotherapy fields as determined by the investigator, or
Show all 29Show fewer
  • Histologic confirmation of tumor through biopsy or resection, or
  • Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and enrollment
  • The recurrent GBM must be potentially-resectable with the intent to resect such that residual tumor rim is less than 1 cm enhancing disease
  • The recurrent GBM must have the appropriate dimensions to allow a Xoft applicator balloon to fit into the tumor cavity
  • Subject has prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent of lower doses. Patients who have received prior treatment with non-standard RT dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible as long as the criterion in 5. is met or approved by principal investigator.
  • Subjects who have undergone CNS related core or needle biopsies, a minimum of 7 days must have elapsed prior to registration
  • History/physical examination, including neurologic examination, within 14 days prior to enrollment (i.e. date the informed consent was signed by the patient)
  • Subject must be ≥ 18 years of age
  • Subject must have a Karnofsky Performance Score ≥ 60%
  • Subject will have had a CBC/differential obtained within 14 days prior to enrollment , with adequate bone marrow function, i.e.:
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 e) Platelets ≥ 75,000 cells/mm3 f) Hemoglobin ≥ 9.0 g/dl (The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable.)
  • Subjects liver and renal function test should reflect adequate hepatic and renal function 14 days prior to enrollment, i.e.:
  • Total bilirubin ≤ 2.0 mg/dL, and SGOT or AST ≤ 2.5 times the upper limit of normal
  • Serum creatinine ≤ 1.8 mg/dL) within 14 days prior to enrollment
  • Subject urine protein level must reflect the following requirements within 14 days before enrollment:
  • Urine protein: creatinine (UPC ) ratio < 1.0 OR
  • Urine dipstick for proteinuria ≤ 2+ (patients who have > 2+ proteinuria on dipstick urinalysis at baseline, must have an UPC ratio <1.0 to be eligible. If the UPC ratio is ≥ 1.0, subsequent 24 hrs urine collection must be ≤ 1 g protein in 24 hrs)
  • Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
  • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 14 days prior to enrollment.
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of treatment
  • Subjects of child-bearing potential must agree to use adequate contraceptive precautions and not to breastfeed (if applicable) until six months after the end of the treatment with Bevacizumab.
  • Patient is planned to have surgery for recurrent Glioblastoma

Who cannot join

  • Subject has had more than three relapses
  • Subject has multi-centric disease
  • Subject has tumors in or near (less than 10mm from tumor margin) critical brain structures, that would exclude sufficient dose delivery to the tumor margin:
  • Optic Chiasm
  • Optic Nerve
  • Subject has infratentorial, or leptomeningeal evidence of recurrent disease
Show all 27Show fewer
  • Subject has recurrent or persistent tumor greater than 6 cm in maximum diameter
  • Subject underwent prior therapy with an inhibitor of VEGF or VEGFR (including Bevacizumab)
  • Subject suffered from prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
  • Women who are pregnant or nursing. Women with child-bearing potential or sexually active men that are not willing/able to use medically acceptable forms of contraception.
  • Subject has contraindications for MRI with or without gadolinium.
  • Subject has contraindications for anesthesia or surgery.
  • Subject is on another therapeutic clinical trial concurrently.
  • Subject suffers severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to enrollment
  • Transmural myocardial infarction within the last 6 months prior to enrollment
  • History of stroke or transient ischemic attack within 6 months prior to enrollment
  • Significant vascular (aortic) disease or clinically significant peripheral vascular disease
  • Active venous or arterial thromboembolic disease
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Laboratory tests for liver function other than screening panel coagulation parameters are not required for entry into this protocol
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. HIV testing is not required for entry into this protocol.
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Subject has history of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to enrollment
  • Subject suffers from gastrointestinal bleeding or any other hemorrhage /bleeding event CTCAE v.5 grade 3 or greater within 30 days prior to enrollment
  • Subject suffers from Hypersensitivity to Bevacizumab

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Providence Saint John's Health Center

    Santa Monica, California, 90404

Other trials in United States

About this study

Official title: Phase II Study of Patients With Recurrent Glioblastoma Multiforme Treated With Maximal Safe Neurosurgical Resection and Intra-Operative Radiation Therapy (IORT) Using the Xoft Axxent Electronic Brachytherapy System and Bevacizumab

The purpose of this trial is to assess the overall survival of patients treated with the Xoft Axxent eBx System and post-radiation adjuvant Bevacizumab for single-fraction IORT following maximal neurosurgical resection of recurrent glioblastoma. A historical comparison will be made to the results of the EBRT + Bevacizumab arm of RTOG 1205.

Read the detailed description

The rationale for IORT, as the sole radiation therapy following surgical resection of recurrent GBM is to expand upon the favorable preliminary results in feasibility, safety and efficacy outcomes obtained at the European Medical Center Study Group (EMC Study Group). The rationale to add Bevacizumab as a systemic treatment is to target radio-resistant and highly tumorigenic cancer stem cells as well as to benefit from its radioprotective effects, i.e. reducing risk of radiation necrosis. Lastly, using Bevacizumab as a systemic therapy will enable the comparison of the results to the historic control arm, the EBRT arm of RTOG 1205.

Being tested
Radiation: Intra-operative Radiation Therapy - IORT, Bevacizumab
Keywords
Bevacizumab, Glioblastoma, Recurrent Glioblastoma, GBM, Recurrent GBM, IORT, Intra-Operative Radiation Therapy, Avastin
Medical subject headings
Glioblastoma

What participants receive

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

  • Radiation: Intra-operative Radiation Therapy - IORTRadiation

    Single fraction, Intra-operative Radiation Therapy at the time of surgical resection of recurrent GBM followed by Bevacizumab 28-56 days after surgery.

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab

Study groups in NCT04681677
Study groupRoleWhat they receive
Experimental: Intra-operative Radiation Therapy - IORTExperimentalRadiation: Intra-operative Radiation Therapy - IORT
Receives: Radiation: Radiation: Intra-operative Radiation Therapy - IORT; Drug: Bevacizumab

What is being measured

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

  1. median overall survival (mOS)

    The median overall survival (mOS) of subjects treated with the Xoft Axxent Electronic Brachytherapy (eBx)® System when used for single-fraction, intra-operative radiation therapy (IORT) following maximal safe neurosurgical resection of recurrent glioblastoma and bevacizumab and compare it to the EBRT + Bevacizumab arm of RTOG 1205.

    Measured: 3 Years

Secondary outcomes (5)
  1. 6 Month rate progression-free survival (PFS)

    To assess progression-free survival and compare it to the EBRT + Bevacizumab arm of RTOG 1205.

    Measured: 6 Month

  2. tumor progression at four weeks

    To assess the tumor progression in the first four weeks after surgery

    Measured: 4 Weeks

  3. Local and distant progression-free survival

    To assess local and distant progression free survival

    Measured: 3 Years

  4. Quality of Life and radiation-related neurotoxicity

    To assess Quality of Life (QOL) and radiation-related neurotoxicity and compare it to the EBRT + Bevacizumab arm of RTOG 1205.

    Measured: 3 Years

  5. Rate of adverse events/safety

    To assess the rate of adverse events/ safety and compare it to the EBRT + Bevacizumab arm of RTOG 1205

    Measured: 3 Years

Timeline

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

  1. First posted23 Dec 2020
  2. Study start2 Nov 2021
  3. Primary completion24 Apr 2024
  4. Study completion24 Apr 2024

Why it stopped: unspecified business decision

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm, prospective, multi-center, non-randomized, historical control, non-inferiority study of subjects treated with single fraction, Intra-Operative Radiation Therapy at the time of maximal resection for recurrent GBM. Treatment with Bevacizumab will be initiated 28-56 days after surgery depending on surgical wound healing assessment at the discretion of the treating investigator.
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04681677
Sponsor's protocol ID
CTPR-0017
Acronym
IORT
Status last verified
Apr 2024
First submitted
17 Dec 2020
Last updated
26 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No: No IPD will be shared

Publications

  • Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9.

    PubMed 27157931
  • Stupp R, Tonn JC, Brada M, Pentheroudakis G; ESMO Guidelines Working Group. High-grade malignant glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010 May;21 Suppl 5:v190-3. doi: 10.1093/annonc/mdq187. No abstract available.

    PubMed 20555079
  • Goryaynov SA, Gol'dberg MF, Golanov AV, Zolotova SV, Shishkina LV, Ryzhova MV, Pitskhelauri DI, Zhukov VY, Usachev DY, Belyaev AY, Kondrashov AV, Shurkhay VA, Potapov AA. [The phenomenon of long-term survival in glioblastoma patients. Part I: the role of clinical and demographic factors and an IDH1 mutation (R 132 H)]. Zh Vopr Neirokhir Im N N Burdenko. 2017;81(3):5-16. doi: 10.17116/neiro20178135-16. Russian.

    PubMed 28665384
  • Haj A, Doenitz C, Schebesch KM, Ehrensberger D, Hau P, Putnik K, Riemenschneider MJ, Wendl C, Gerken M, Pukrop T, Brawanski A, Proescholdt MA. Extent of Resection in Newly Diagnosed Glioblastoma: Impact of a Specialized Neuro-Oncology Care Center. Brain Sci. 2017 Dec 25;8(1):5. doi: 10.3390/brainsci8010005.

    PubMed 29295569
  • Hardesty DA, Sanai N. The value of glioma extent of resection in the modern neurosurgical era. Front Neurol. 2012 Oct 18;3:140. doi: 10.3389/fneur.2012.00140. eCollection 2012.

    PubMed 23087667
  • Krivoshapkin AL, Sergeev GS, Gaytan AS, Kurbatov VP, Kalneus LE, Tarantsev EG. New software for objective evaluation of brain glioblastoma resection degree. Zh Vopr Neirokhir Im N N Burdenko. 2014;78(5):33-9; discussion 40. English, Russian.

    PubMed 25406906
  • Davis ME. Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs. 2016 Oct 1;20(5 Suppl):S2-8. doi: 10.1188/16.CJON.S1.2-8.

    PubMed 27668386
  • Gaspar LE, Fisher BJ, Macdonald DR, LeBer DV, Halperin EC, Schold SC Jr, Cairncross JG. Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys. 1992;24(1):55-7. doi: 10.1016/0360-3016(92)91021-e.

    PubMed 1512163
  • Choucair AK, Levin VA, Gutin PH, Davis RL, Silver P, Edwards MS, Wilson CB. Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas. J Neurosurg. 1986 Nov;65(5):654-8. doi: 10.3171/jns.1986.65.5.0654.

    PubMed 3021931
  • Mallick S, Benson R, Hakim A, Rath GK. Management of glioblastoma after recurrence: A changing paradigm. J Egypt Natl Canc Inst. 2016 Dec;28(4):199-210. doi: 10.1016/j.jnci.2016.07.001. Epub 2016 Jul 28.

    PubMed 27476474
  • Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Le Rhun E, Balana C, Chinot O, Bendszus M, Reijneveld JC, Dhermain F, French P, Marosi C, Watts C, Oberg I, Pilkington G, Baumert BG, Taphoorn MJB, Hegi M, Westphal M, Reifenberger G, Soffietti R, Wick W; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017 Jun;18(6):e315-e329. doi: 10.1016/S1470-2045(17)30194-8. Epub 2017 May 5.

    PubMed 28483413
  • van Linde ME, Brahm CG, de Witt Hamer PC, Reijneveld JC, Bruynzeel AME, Vandertop WP, van de Ven PM, Wagemakers M, van der Weide HL, Enting RH, Walenkamp AME, Verheul HMW. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol. 2017 Oct;135(1):183-192. doi: 10.1007/s11060-017-2564-z. Epub 2017 Jul 20.

    PubMed 28730289
  • Ringel F, Pape H, Sabel M, Krex D, Bock HC, Misch M, Weyerbrock A, Westermaier T, Senft C, Schucht P, Meyer B, Simon M; SN1 study group. Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro Oncol. 2016 Jan;18(1):96-104. doi: 10.1093/neuonc/nov145. Epub 2015 Aug 4.

    PubMed 26243790
  • Landy HJ, Feun L, Schwade JG, Snodgrass S, Lu Y, Gutman F. Retreatment of intracranial gliomas. South Med J. 1994 Feb;87(2):211-4. doi: 10.1097/00007611-199402000-00013.

    PubMed 8115886
  • Ammirati M, Galicich JH, Arbit E, Liao Y. Reoperation in the treatment of recurrent intracranial malignant gliomas. Neurosurgery. 1987 Nov;21(5):607-14. doi: 10.1227/00006123-198711000-00001.

    PubMed 2827051

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiation: Intra-operative Radiation Therapy - IORT and Bevacizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Xoft, Inc. at 1 site 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 29 inclusion and 27 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 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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: unspecified business decision). 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?

median overall survival (mOS) (time frame: 3 Years). 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 NCT04681677, which also lists 23 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 26 Apr 2024.

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