Malignant GliomaPhase 2NCT04197492
Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas
A Phase 2 study testing Hypofractionated Stereotactic Radiotherapy and Anlotinib in people with Malignant Glioma, run by Huashan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- Hypofractionated Stereotactic Radiotherapy and Anlotinib
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 16 Dec 2019to 31 Dec 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-70 years of age;
- Karnofsky performance status (KPS) ≥ 60;
- Original histopathologically proven diagnosis World Health Organization (WHO) Grade 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
CyberKnife Center, Department of Neurosurgery, Huashan Hospital
Shanghai, Shanghai Municipality, 200040
About this study
Official title: A Phase II Study of Hypofractionated Stereotactic Radiotherapy Combined With Anlotinib in Patients With Recurrent High-Grade Glioma
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.
Read the 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.
- Conditions
- Malignant Glioma
- Being tested
- Hypofractionated Stereotactic Radiotherapy, Anlotinib
- Keywords
- Hypofractionated Stereotactic Radiotherapy, Recurrent High-grade Glioma, Anlotinib
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypofractionated Stereotactic RadiotherapyRadiation
Also called Hypofractionated Stereotactic Radiosurgery
Hypofractionated stereotactic radiotherapy (CyberKnife, 25Gy/5fx)
AnlotinibDrug
Also called AL3818
Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| HSRT With Anlotinib | Experimental | * 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. Receives: Radiation: Hypofractionated Stereotactic Radiotherapy; Drug: Anlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Estimated using the Kaplan-Meier method
Measured: From the start of treatment to the date of death or the last follow-up, up to approximately 24 months
Secondary outcomes (5)
Progression-free survival (PFS)
Estimated using the Kaplan-Meier method
Measured: From the start of treatment to the date of disease progression or death, up to approximately 24 months
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.
Measured: Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
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.
Measured: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
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.
Measured: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
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.
Measured: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2019
- Study start16 Dec 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Huashan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chongbo Zhao, Huashan Hospital
- Investigators
- Enmin Wang, MD, Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04197492
- Sponsor's protocol ID
- KY2019-525
- Other IDs
- HSCK-002
- Status last verified
- Jan 2024
- First submitted
- 11 Dec 2019
- Last updated
- 5 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25104067Clarke 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.
PubMed 28870792Minniti 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.
PubMed 23129347Guan 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.
PubMed 35448002
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Hypofractionated Stereotactic Radiotherapy Combined With Anlotinib in Patients With Recurrent High-Grade Glioma
- ClinicalTrials.gov ID
- NCT04197492
- Acronym / sponsor ID
- KY2019-525
- Conditions
- Malignant Glioma
- Keywords
- Hypofractionated Stereotactic Radiotherapy, Recurrent High-grade Glioma, Anlotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 13 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSRT With Anlotinib | Experimental | Radiation: Hypofractionated Stereotactic Radiotherapy, Drug: Anlotinib* 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 18-70 years of age;
- Karnofsky performance status (KPS) ≥ 60;
- Original histopathologically proven diagnosis World Health Organization (WHO) Grade 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypofractionated Stereotactic RadiotherapyAlso: Hypofractionated Stereotactic RadiosurgeryHypofractionated stereotactic radiotherapy (CyberKnife, 25Gy/5fx) | Radiation | HSRT With Anlotinib |
| AnlotinibAlso: AL3818Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle. | Drug | HSRT With Anlotinib |
Primary outcome
Overall survival (OS)
Time frame: From the start of treatment to the date of death or the last follow-up, up to approximately 24 months
Estimated using the Kaplan-Meier method
5 secondary outcomes
Progression-free survival (PFS)
Time frame: From the start of treatment to the date of disease progression or death, up to approximately 24 months
Objective response rate (ORR)
Time frame: Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
Quality of Life score (QoL): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0
Time frame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Cognitive function
Time frame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Toxicity rate
Time frame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Background: PubMed 25104067Wuthrick 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.
- Background: PubMed 28870792Clarke 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.
- Background: PubMed 23129347Minniti 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.
- Derived from this study: PubMed 35448002Guan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Enmin Wang, MD principal investigator
Huashan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hypofractionated Stereotactic Radiotherapy and Anlotinib in people with Malignant Glioma, run by Huashan Hospital at 1 site in China.
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 9 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 5 Jan 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 China. 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?
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?
Overall survival (OS) (time frame: From the start of treatment to the date of death or the last follow-up, up to approximately 24 months). 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 NCT04197492, which also lists 4 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 5 Jan 2024.