Brain NeoplasmPhase 1NCT02672995
Fractionated Stereotactic Radiosurgery With Concurrent Bevacizumab for Brain Metastases: A Phase I Dose-escalation Trial
A Phase 1 study testing Fractionated stereotactic radiosurgery and bevacizumab in people with Brain Neoplasm, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The investigators propose a new treatment strategy of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases. This phase I dose-escalation study is to establish the feasibility of this strategy and find the recommended doses. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Brain Neoplasm
- What is being tested?
- Fractionated stereotactic radiosurgery and bevacizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2018to Dec 2018
- Phase
- Phase 1
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for inclusion, patients must fulfill the following criteria:
- Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of measurable brain metastases (1.5~3.5 cm).
- The number of brain metastases receiving fractionated SRS: ≤3.
- No evidence of leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration.
- Age ≥ 20 years.
- Karnofsky Performance Status ≥ 60.
Show all 28Show fewer
- Life expectancy of ≥ 4 months.
- Women of childbearing potential and male participants must practice adequate contraception.
- Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent.
- Exclusion criteria Patients fulfill any of the following criteria will be excluded from this trial
- Serum creatinine > 2.0 mg/dL within 30 days prior registration
- Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies, severe claustrophobia
- Patients with evidence of bleeding diathesis or coagulopathy, international normalized ratio (INR) >1.5
- Patients who require the use of warfarin sodium > 1 mg
- Patients with active GI ulcers, GI bleeding, or active inflammatory bowel disease
- Patients with clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >160/90 mmHg on medication], history of myocardial infarction or unstable angina within 12 months of registration), New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are not eligible
- Patients with a history of aneurysms, cerebrovascular accident (CVA) and arteriovenous malformations
- Patients with arterial thromboembolic events, including transient ischemic attack (TIA), or clinically significant peripheral artery disease within 6 months of registration
- Patients with serious, non-healing wound, ulcer, or current healing fracture
- Patients with a history of any type of fistula (vesicovaginal, gastrointestinal, etc) or gastrointestinal perforation
- Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
- Uncontrolled active infection requiring intravenous antibiotics at the time of registration
- Transmural myocardial infarction ≤ 6 months prior to registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Uncontrolled psychiatric disorder
- Will receive any other investigational agent or chemotherapy and/or target therapies during SRS
- Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Chia-Chun Wang, MD contact
Feng-Ming Hsu contact
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100
Chia-Chun Wang, chiachun@ntuh.gov.tw
About this study
The investigators propose a new treatment strategy of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases. This phase I dose-escalation study is to establish the feasibility of this strategy and find the recommended doses.
Read the detailed description
For each group (two groups according to tumor size), the design proceeds with cohorts of three patients, with the first cohort treated at a starting dose. If none of the three patients in a cohort experiences a dose-limiting toxicity (DLT), the next cohort with three patients will be treated at the next higher dose level. If one of the first three patients experiences a dose-limiting toxicity, the next cohort will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLTs and the maximum tolerated dose (MTD) will be the dose level just below. If the highest planned dose was achieved without two patients experiencing DLTs, the MTD will be that dose level.
The DLT is defined as grade 4 or above toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 within 4 months after stereotactic radiosurgery (SRS):
Grade 4 central nervous system necrosis (life-threatening consequences; urgent intervention indicated) Grade 4 sensory or motor neuropathy (life-threatening consequences; urgent intervention indicated) Grade 4 hemorrhage (life-threatening consequences; urgent intervention indicated) or Grade 4 thromboembolic event (life-threatening consequences such as pulmonary embolism, cerebrovascular event, arterial insufficiency; hemodynamic or neurologic instability; urgent intervention indicated) Grade 4 hypertension (life-threatening consequences such as malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis; urgent intervention indicated)
Study treatment:
Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.
- Conditions
- Brain Neoplasm
- Being tested
- Fractionated stereotactic radiosurgery, bevacizumab
- Keywords
- stereotactic radiosurgery,Bevacizumab
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fractionated stereotactic radiosurgeryRadiation
Also called Fractionated SRS
Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
bevacizumabDrug
Also called Avastin
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.
| Study group | Role | What they receive |
|---|---|---|
| Single arm dose-escalation | Experimental | Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab. Receives: Radiation: Fractionated stereotactic radiosurgery; Drug: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
The maximum tolerated dose of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases.
Measured: 4 months
Secondary outcomes (3)
Response rate
Response rate
Measured: 4 months
Time to progression
Time to progression
Measured: 4 months
The incidence of radiation-induced adverse effects
The incidence of radiation-induced adverse effects
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2016 (estimated)
- Study startJan 2018 (estimated)
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain NeoplasmStudies of the same condition, open and under way.
- More trials run by National Taiwan University 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chia-Chun Wang, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02672995
- Sponsor's protocol ID
- 201511005MINB
- Status last verified
- Aug 2017
- First submitted
- 28 Jan 2016
- Last updated
- 18 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fractionated Stereotactic Radiosurgery With Concurrent Bevacizumab for Brain Metastases: A Phase I Dose-escalation Trial
- ClinicalTrials.gov ID
- NCT02672995
- Acronym / sponsor ID
- 201511005MINB
- Conditions
- Brain Neoplasm
- Keywords
- stereotactic radiosurgery,Bevacizumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Jan 2018 (estimated)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 3 Feb 2016 (estimated)
- 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.
The investigators propose a new treatment strategy of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases. This phase I dose-escalation study is to establish the feasibility of this strategy and find the recommended doses.
Detailed description
For each group (two groups according to tumor size), the design proceeds with cohorts of three patients, with the first cohort treated at a starting dose. If none of the three patients in a cohort experiences a dose-limiting toxicity (DLT), the next cohort with three patients will be treated at the next higher dose level. If one of the first three patients experiences a dose-limiting toxicity, the next cohort will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLTs and the maximum tolerated dose (MTD) will be the dose level just below. If the highest planned dose was achieved without two patients experiencing DLTs, the MTD will be that dose level.
The DLT is defined as grade 4 or above toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 within 4 months after stereotactic radiosurgery (SRS):
Grade 4 central nervous system necrosis (life-threatening consequences; urgent intervention indicated) Grade 4 sensory or motor neuropathy (life-threatening consequences; urgent intervention indicated) Grade 4 hemorrhage (life-threatening consequences; urgent intervention indicated) or Grade 4 thromboembolic event (life-threatening consequences such as pulmonary embolism, cerebrovascular event, arterial insufficiency; hemodynamic or neurologic instability; urgent intervention indicated) Grade 4 hypertension (life-threatening consequences such as malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis; urgent intervention indicated)
Study treatment:
Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm dose-escalation | Experimental | Radiation: Fractionated stereotactic radiosurgery, Drug: bevacizumabFractionated stereotactic radiosurgery: Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break. Concurrent bevacizumab: Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of measurable brain metastases (1.5~3.5 cm).
- The number of brain metastases receiving fractionated SRS: ≤3.
- No evidence of leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration.
- Age ≥ 20 years.
- Karnofsky Performance Status ≥ 60.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Fractionated stereotactic radiosurgeryAlso: Fractionated SRSFractionated stereotactic radiosurgery: Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break. | Radiation | Single arm dose-escalation |
| bevacizumabAlso: AvastinConcurrent bevacizumab: Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab. | Drug | Single arm dose-escalation |
Primary outcome
Maximum tolerated dose
Time frame: 4 months
The maximum tolerated dose of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases.
3 secondary outcomes
Response rate
Time frame: 4 months
Time to progression
Time frame: 4 months
The incidence of radiation-induced adverse effects
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2017.
- Individual participant dataSharing planned: Undecided
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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.
Chia-Chun Wang, MD contact
Feng-Ming Hsu contact
Chia-Chun Wang principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fractionated stereotactic radiosurgery and bevacizumab in people with Brain Neoplasm, run by National Taiwan University Hospital at 1 site in Taiwan.
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 28 inclusion and 0 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 18 Aug 2017. 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 Taiwan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Chia-Chun Wang, MD (chiachun@ntuh.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Aug 2017.