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Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas

Primary Purpose

Malignant Glioma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Hypofractionated Stereotactic Radiotherapy

Anlotinib

About this trial

This is an interventional treatment trial for Malignant Glioma focused on measuring Hypofractionated Stereotactic Radiotherapy, Recurrent High-grade Glioma, Anlotinib

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

18-70 years of age;
Karnofsky performance status (KPS) ≥ 60;
Original histopathologically proven diagnosis World Health Organization (WHO) Grade 3/4 glioma;
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;
Measurable disease;
Estimated survival of at least 3 months;
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;
Signed informed consent form;
Agreed to participate the follow-up.

Exclusion Criteria:

Prior invasive malignancy unless disease free;
Received re-irradiation;
More than 3 relapses or evidence of subtentorial recurrent disease or tumor greater than 6 cm in maximum diameter;
Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR;
Pregnancy or or nursing mothers;
Participated in other trials after diagnosis of recurrent;
Influence factors toward oral medications;
Patients with CTCAE5.0 grade 3+ bleeding;
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%;
Long-term unhealed wounds or fractures;
History of organ transplantation;
Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.

Sites / Locations

CyberKnife Center, Department of Neurosurgery, Huashan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HSRT With Anlotinib

Arm Description

Hypofractionated stereotactic radiotherapy using CyberKnife 25Gy/5fx, 5 days a week for 1 week. Anlotinib once daily (12mg/d) orally administered on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.

Outcomes

Primary Outcome Measures

Overall survival (OS)

Estimated using the Kaplan-Meier method

Secondary Outcome Measures

Progression-free survival (PFS)

Estimated using the Kaplan-Meier method

Objective response rate (ORR)

ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Assessment in Neuro-Oncology (RANO) prior to progression or any further therapy.

Quality of Life score (QoL): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0

EORTC QLQ-C30 (version 3.0) questionnaire to evaluate the quality of life. All scales range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Cognitive function

Mini-Mental State Exam (MMSE, score range 0 to 30) to evaluate the cognitive function. Any score of 24 or more (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.

Toxicity rate

Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the toxicity. Estimated using an exact binomial distribution together with 95% confidence interval.

Full Information

NCT ID

NCT04197492

First Posted

December 11, 2019

Last Updated

December 15, 2019

Sponsor

Huashan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04197492

Brief Title

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

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 16, 2019 (Actual)

Primary Completion Date

December 15, 2021 (Anticipated)

Study Completion Date

December 15, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Huashan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Glioma

Keywords

Hypofractionated Stereotactic Radiotherapy, Recurrent High-grade Glioma, Anlotinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HSRT With Anlotinib

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Hypofractionated Stereotactic Radiotherapy

Other Intervention Name(s)

Hypofractionated Stereotactic Radiosurgery

Intervention Description

Hypofractionated stereotactic radiotherapy (CyberKnife, 25Gy/5fx)

Intervention Type

Drug

Intervention Name(s)

Anlotinib

Other Intervention Name(s)

AL3818

Intervention Description

Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle.

Primary Outcome Measure Information:

Title

Overall survival (OS)

Description

Estimated using the Kaplan-Meier method

Time Frame

From the start of treatment to the date of death or the last follow-up, up to approximately 24 months

Secondary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

Estimated using the Kaplan-Meier method

Time Frame

From the start of treatment to the date of disease progression or death, up to approximately 24 months

Title

Objective response rate (ORR)

Description

Time Frame

Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months

Title

Quality of Life score (QoL): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0

Description

Time Frame

Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months

Title

Cognitive function

Description

Time Frame

Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months

Title

Toxicity rate

Description

Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the toxicity. Estimated using an exact binomial distribution together with 95% confidence interval.

Time Frame

Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 18-70 years of age; Karnofsky performance status (KPS) ≥ 60; Original histopathologically proven diagnosis World Health Organization (WHO) Grade 3/4 glioma; 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; Measurable disease; Estimated survival of at least 3 months; 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; Signed informed consent form; Agreed to participate the follow-up. Exclusion Criteria: Prior invasive malignancy unless disease free; Received re-irradiation; More than 3 relapses or evidence of subtentorial recurrent disease or tumor greater than 6 cm in maximum diameter; Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR; Pregnancy or or nursing mothers; Participated in other trials after diagnosis of recurrent; Influence factors toward oral medications; Patients with CTCAE5.0 grade 3+ bleeding; 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%; Long-term unhealed wounds or fractures; History of organ transplantation; Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yun Guan, MD

Phone

+86 15301987553

yguan10@fudan.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Xin Wang, MD

Phone

+86 13120557273

wangxinck@fudan.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Enmin Wang, MD

Organizational Affiliation

Huashan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

CyberKnife Center, Department of Neurosurgery, Huashan Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200040

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Enmin Wang, MD

wangem@fudan.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25104067

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.

Results Reference

background

PubMed Identifier

28870792

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.

Results Reference

background

PubMed Identifier

23129347

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.

Results Reference

background

PubMed Identifier

35448002

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.

Results Reference

derived

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Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas

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