Clinical trial NCT04547621: HSRT and IMRT Chemoradiotherapy for Newly Diagnosed GBM
Official title: The Combination of Hypofractionated Stereotactic Radiotherapy and Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme: A Prospective, Single-Center, Single-Arm Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Glioma, Malignant
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2020-09-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the safety and effectiveness of the combination of 30Gy/5fx HSRT and 20Gy/10fx IMRT adjuvant therapy. The total biological effective dose (BED) of the PTV is 72 Gy in a ratio of alpha/beta ratio of 3, which equals to the conventional 60Gy/30fx treatment. This study can provide evidence for future non-inferiority phase III randomized controlled trials. The abbreviated course of radiotherapy can reduce the treatment time by half, benefit patients, and utilize the health resource.


Eligibility criteria: Inclusion Criteria:

1. 18-70 years of age;
2. Karnofsky performance status (KPS) ≥ 60 within 14 days prior to registration;
3. Histopathologically proved diagnosis glioblastoma multiforme;
4. Underwent surgery, gross total resection or subtotal resection;
5. Estimated survival of at least 3 months;
6. Hgb \> 90/gL; absolute neutrophil count (ANC) \> 1.5×109/L, platelets \> 80×109/L; Creatinine \< 1.5 times the upper limit of laboratory normal value; Bilirubin \< 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) \< 3 times the upper limit of laboratory normal value;
7. Signed informed consent form;
8. Agreed to participate in the follow-up.

Exclusion Criteria:

1. Prior invasive malignancy unless disease free;
2. Received irradiation or other anti-tumor adjuvant therapies;
3. Brain stem disease or tumor greater than 6 cm in maximum diameter;
4. Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR;
5. Pregnancy or nursing mothers;
6. Participated in other trials after diagnosis;
7. Influence factors toward oral medications;
8. Patients with CTCAE5.0 grade 3+ bleeding within 4 weeks prior to registration;
9. Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) \<50%;
10. Long-term unhealed wounds or fractures;
11. History of organ transplantation;
12. Serious diseases that endanger patients' safety or affect patients' completion of research, according to the researchers' judgment.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From the start of treatment to the date of death or the last follow-up, up to approximately 24 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From the start of treatment to the date of disease progression or death, up to approximately 24 months
measure: Objective response rate (ORR)
timeFrame: Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
measure: Quality of Life score (QoL)
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
measure: Cognitive function
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
measure: Toxicity rate
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: CyberKnife Center, Department of Neurosurgery, Huashan Hospital
state: Shanghai
Study officials:
affiliation: CyberKnife Center, Department of Neurosurgery, Huashan Hospital
name: Enmin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
citation: Martinez-Carrillo M, Tovar-Martin I, Zurita-Herrera M, Del Moral-Avila R, Guerrero-Tejada R, Saura-Rojas E, Osorio-Ceballos JL, Arrebola-Moreno JP, Exposito-Hernandez J. Salvage radiosurgery for selected patients with recurrent malignant gliomas. Biomed Res Int. 2014;2014:657953. doi: 10.1155/2014/657953. Epub 2014 May 7.
citation: Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremic B, Rosenblatt E, Fidarova E. International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme. J Clin Oncol. 2015 Dec 10;33(35):4145-50. doi: 10.1200/JCO.2015.62.6606. Epub 2015 Sep 21.
citation: Guan Y, Pan M, Yang J, Lu Q, Han L, Liu Y, Li J, Zhu H, Gong X, Mei G, Liu X, Pan L, Dai J, Wang Y, Wang E, Wang X. A phase II open label, single arm study of hypofractionated stereotactic radiotherapy with chemoradiotherapy using intensity-modulated radiotherapy for newly diagnosed glioblastoma after surgery: the HSCK-010 trial protocol. BMC Cancer. 2022 Jul 29;22(1):827. doi: 10.1186/s12885-022-09914-5.