Clinical trial NCT04197492: Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas
Official title: A Phase II Study of Hypofractionated Stereotactic Radiotherapy Combined With Anlotinib in Patients With Recurrent High-Grade Glioma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Malignant Glioma
Keywords: Hypofractionated Stereotactic Radiotherapy
Recurrent High-grade Glioma
Anlotinib
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2019-12-13
Enrollment: 22
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: A Phase II Study of Hypofractionated Stereotactic Radiotherapy (HSRT) With Anlotinib in Patients With Recurrent High-Grade Glioma. The primary endpoint is overall survival after radiotherapy. Secondary endpoints included progress-free survival, objective response rate, cognitive function, quality of life, toxicity.

Detailed description: Original histopathologically proven diagnosis World Health Organization (WHO) Grade 3/4 glioma patients who underwent surgery, chemoradiotherapy and adjuvant chemotherapy (Stupp Protocol). Recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or histopathology. Intervention included CyberKnife hypofractionated stereotactic radiotherapy (25Gy/5fx) with Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle.

Eligibility criteria: Inclusion Criteria:

1. 18-70 years of age;
2. Karnofsky performance status (KPS) ≥ 60;
3. Original histopathologically proven diagnosis World Health Organization (WHO) Grade 4 glioma;
4. Underwent surgery, chemoradiotherapy and adjuvant chemotherapy (Stupp Protocol) after initial diagnosis, recurrent based on the Response Assessment in Neuro-Oncology (RANO) criteria and/or histopathologically proven;
5. Measurable disease;
6. Estimated survival of at least 3 months;
7. Hgb \> 9 gm; absolute neutrophil count (ANC) \> 1500/μl; platelets \> 100,000; 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;
8. Signed informed consent form;
9. Agreed to participate the follow-up.

Exclusion Criteria:

1. Prior invasive malignancy unless disease free;
2. Received re-irradiation;
3. More than 3 relapses or evidence of subtentorial recurrent 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 or nursing mothers;
6. Participated in other trials after diagnosis of recurrent;
7. Influence factors toward oral medications;
8. Patients with CTCAE5.0 grade 3+ bleeding;
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): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0
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: Huashan Hospital
name: Enmin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wuthrick EJ, Curran WJ Jr, Camphausen K, Lin A, Glass J, Evans J, Andrews DW, Axelrod R, Shi W, Werner-Wasik M, Haacke EM, Hillman GG, Dicker AP. A pilot study of hypofractionated stereotactic radiation therapy and sunitinib in previously irradiated patients with recurrent high-grade glioma. Int J Radiat Oncol Biol Phys. 2014 Oct 1;90(2):369-75. doi: 10.1016/j.ijrobp.2014.05.034. Epub 2014 Aug 4.
citation: Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):797-804. doi: 10.1016/j.ijrobp.2017.06.2466. Epub 2017 Jun 30.
citation: Minniti G, Scaringi C, De Sanctis V, Lanzetta G, Falco T, Di Stefano D, Esposito V, Enrici RM. Hypofractionated stereotactic radiotherapy and continuous low-dose temozolomide in patients with recurrent or progressive malignant gliomas. J Neurooncol. 2013 Jan;111(2):187-94. doi: 10.1007/s11060-012-0999-9. Epub 2012 Nov 6.
citation: Guan Y, Li J, Gong X, Zhu H, Li C, Mei G, Liu X, Pan L, Dai J, Wang Y, Wang E, Liu Y, Wang X. Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at the First Recurrence: A Preliminary Report. Brain Sci. 2022 Apr 2;12(4):471. doi: 10.3390/brainsci12040471.