Brain MetastasesPhase 1NCT02080949
Phase I Dose Escalation in Patients With 1-3 Unresectable Brain Metastases
A Phase 1 study testing 4fx x 5Gy in people with Brain Metastases, run by Barretos Cancer Hospital at 1 site in Brazil.
Trial summary
Brain metastases occur in 20-40% of patients with metastatic cancer. The standard treatment is based on whole brain radiation therapy and local treatment of metastases as neurosurgery or radiosurgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- 4fx x 5Gy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2011to Oct 2011
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with 1-3 brain metastases with histological diagnosis of malignancy and ineligible for surgery or RS
- Age ≥18 years
- Karnofsky Performance Status (KPS) ≥ 70%
- "Status" of neurological function: zero to 3
- Anticipated survival > 3 months
- Informed consent for this research signed
Who cannot join
- Prior brain irradiation for any reason
- Indian race
- Primary tumor of lymphoma, leukemia, germ cell, small cell carcinoma or central nervous system
- Leptomeningeal dissemination
- single or multiple metastases with surgical (patients with KPS ≥ 70, with metastatic site in an area not eloquent or herniation causing mass effect or hydrocephalus) or RS indication(patients with KPS ≥ 70 and metastatic lesion <4 cm in diameter with distance to chiasm, tract and optic nerves, and brain stem > 5 mm)
- Inability to have MRI
Show all 9Show fewer
- Patients who have undergone prior treatment for specific brain metastases (eg surgery, RS, chemotherapy), excluding corticosteroids
- People with mental incapacity
- People in a relationship of dependence as prisoners, soldiers, students, staff, etc..
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Barretos Cancer Hospital - Fundação Pio XII
Barretos, São Paulo, 14784-400
About this study
Official title: Study Phase I Dose Escalation With Hypofractionated Stereotactic Radiotherapy in Patients With 1-3 Unresectable Brain Metastases
Brain metastases occur in 20-40% of patients with metastatic cancer. The standard treatment is based on whole brain radiation therapy and local treatment of metastases as neurosurgery or radiosurgery. However, many cases can not receive a standard local treatment, and local relapse occurs in almost 50% of cases treated with only whole brain irradiation. There are retrospective studies of increased radiation dose at the site of metastasis with hypofractionated stereotactic radiotherapy (HSRT) with favorable results, but there are no controlled studies regarding the safety of radiation dose in these situations. This study is a phase I study to evaluate the maximum tolerance dose (MTD) with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS.
Read the detailed description
RADIOTHERAPY WBRT Patient in supine position Immobilization of the head with a thermoplastic mask Simulation with computed tomography (CT) with contrast.
Design:
Clinical target volume (CTV): brain and meninges to the foramen magnum Planned treatment volume (PTV): 5 mm from the CTV in all directions
- Planning:
- Technique: Two latero-lateral fields, with permission to use field inside the fields, known as "field-in-field".
- Isodose prescription: 95% of the dose covering 95% of PTV
- Maximum dose allowed in the PTV: 15% higher than the prescribed dose
- Dose / fractionation: 30 Gy in 10 fractions of 3 Gy once a day, five times a week
- Treatment Equipment: Linear accelerator of 6-MeV photons (Varian Clinac 600 CD, Varian Medical Systems, Palo Alto, CA, USA)
HSRT Planning HSRT
- Held on the seventh day post-WBRT(or next business day if the date coincides with a weekend or holiday):
- Patient in supine position
- Preparation of individualized mask "Mask Patient One set is 41,100 (BrainLAB AG, Heimstetten, Germany)
- Brain MRI with contrast and volumetric reconstruction of 1 mm without mask and without fiducial markers
- Brain CT with contrast, 1-mm slices with tracking and stereotactic fixation.
- Fusion of MRI and CT in the planning system iPlan version 4.1 (BrainLAB AG, Heimstetten, Germany)
- Delineation Gross tumor volume (GTV): metastasis(es) of the brain displayed in the MRI signal in T1 with contrast Clinical target volume (CTV)= GTV Planning target volume (PTV)= CTV with 3 mm margins in all directions
- Physical Planning
- Technique: multiple dynamic arcs, multiple static conformal fields, multiple static modulated fields, multiple static arcs
- isodose prescription: higher isodose that meets the following criteria: Coverage of at least 95% of the PTV with the prescription dose (V100 ≥ 95%) and 95% Of the prescription dose covering at least 99% of the PTV (V95 ≥ 99%).
- Maximum dose allowed in or outside the PTV: 20% of prescription dose, while respecting the tolerance of the organs described below.
- Scores compliance with RTOG
- Dose escalation scheme
Study model It'll be recruited 3 patients to the initial scheme of 4 fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered the study initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with next dose level. The same criteria of recruitment will be performed till any scheme reach the MTD or up to the scheme of 4 fractions of 9 Gy.
- The number of fractions of HSRT will be kept in 4 fractions for all cohorts.
- The initial dose is 5 Gy per day.
- Increasing the dose of one cohort to another will be more than 1 Gy per day of HSRT. For example: If the scheme of 4 fractions of 5 Gy will not have unacceptable toxicity, the study continues to recruit patients for the scheme of 4 fractions of 6 Gy, and so subsequently.
- The study will recruit patients to the fractionation scheme up to four fractions of 9 Gy according to the BEDGy3 be similar to a maximum dose of RS studies to brain metastasis of 24 Gy in one fraction.
- At the discretion of the responsible investigator for the safety of the study, the number of patients may be increased in each cohort during the study.
- Restrictions of radiation dose on critical organ
- optic chiasm: BEDGy3: 90 Gy
- optic nerves: BEDGy3: 90 Gy
- optic tract: BEDGy3: 90 Gy
- brainstem: BEDGy3: 110 Gy
- retina: BEDGy3: 72 Gy
- lens: BEDGy3: 16.7 Gy
- Simulation of HSRT
- Ten days post-WBRT(or next business day, if the date coincides with a weekend or holiday)
- Tests of collision safety and quality control testing to ensure the alignment of isocenters radiation, mechanical and coincidence of lasers (Winston-Lutz test).
- Treatment of HSRT
- Eleventh day post-WBRT(or next business day, if the date coincides with a weekend or holiday)
- Treatment equipment
- linear accelerator of 6-MeV photons (Varian Clinac linear accelerator 600 CD, Varian Medical Systems, Palo Alto, CA, USA)
- Micromultileaf m3 System(BrainLAB AG, Heimstetten, Germany).
- Conditions
- Brain Metastases
- Being tested
- 4fx x 5Gy
- Keywords
- brain metastases, hypofractionated stereotactic radiotherapy
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4fx x 5GyRadiation
Also called hypofractionated stereotactic radiotherapy
It'll be recruited 3 patients to the initial scheme of 4 fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered the study initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with next dose level. The same criteria of recruitment will be performed till any scheme reach the MTD or up to the scheme of 4 fractions of 9 Gy.
| Study group | Role | What they receive |
|---|---|---|
| HSRT - 4fx x 5 Gy | Experimental | It'll be recruited 3 patients to the initial regimen of four fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered that the study was initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with the next dose level. Receives: Radiation: 4fx x 5Gy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerance Dose
To establish the MTD with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS, and find the dose for phase II study.
Measured: Always after 3 patients recruited (up to 30 days after completion of radiotherapy planned)
Secondary outcomes (2)
Radiotoxicity
CTCAE version 3.0
Measured: Up to 30 days after the end of radiotherapy
Neurocognitive benefit
Estimate the benefit/neurocognitive decline by a battery of tests including the Medical Outcomes Scale-Cognitive Functioning Subscale (MOS); and the Mini-Mental Status Examination (MMSE).
Measured: Baseline and up to 30 days after completion of radiotherapy planned
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2014 (estimated)
- Study startJan 2011
- Primary completionOct 2011
- Study completionOct 2011
Why it stopped: Low rate of recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barretos Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ricardo A Nakamura, MD, Principal investigator, Barretos Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02080949
- Sponsor's protocol ID
- HSRT
- Status last verified
- Mar 2014
- First submitted
- 1 Mar 2014
- Last updated
- 7 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Phase I Dose Escalation With Hypofractionated Stereotactic Radiotherapy in Patients With 1-3 Unresectable Brain Metastases
- ClinicalTrials.gov ID
- NCT02080949
- Acronym / sponsor ID
- HSRT
- Conditions
- Brain Metastases
- Keywords
- brain metastases, hypofractionated stereotactic radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Low rate of recruitment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Barretos Cancer HospitalUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 7 Mar 2014 (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.
Brain metastases occur in 20-40% of patients with metastatic cancer. The standard treatment is based on whole brain radiation therapy and local treatment of metastases as neurosurgery or radiosurgery. However, many cases can not receive a standard local treatment, and local relapse occurs in almost 50% of cases treated with only whole brain irradiation. There are retrospective studies of increased radiation dose at the site of metastasis with hypofractionated stereotactic radiotherapy (HSRT) with favorable results, but there are no controlled studies regarding the safety of radiation dose in these situations. This study is a phase I study to evaluate the maximum tolerance dose (MTD) with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS.
Detailed description
RADIOTHERAPY WBRT Patient in supine position Immobilization of the head with a thermoplastic mask Simulation with computed tomography (CT) with contrast.
Design:
Clinical target volume (CTV): brain and meninges to the foramen magnum Planned treatment volume (PTV): 5 mm from the CTV in all directions
- Planning:
- Technique: Two latero-lateral fields, with permission to use field inside the fields, known as "field-in-field".
- Isodose prescription: 95% of the dose covering 95% of PTV
- Maximum dose allowed in the PTV: 15% higher than the prescribed dose
- Dose / fractionation: 30 Gy in 10 fractions of 3 Gy once a day, five times a week
- Treatment Equipment: Linear accelerator of 6-MeV photons (Varian Clinac 600 CD, Varian Medical Systems, Palo Alto, CA, USA)
HSRT Planning HSRT
- Held on the seventh day post-WBRT(or next business day if the date coincides with a weekend or holiday):
- Patient in supine position
- Preparation of individualized mask "Mask Patient One set is 41,100 (BrainLAB AG, Heimstetten, Germany)
- Brain MRI with contrast and volumetric reconstruction of 1 mm without mask and without fiducial markers
- Brain CT with contrast, 1-mm slices with tracking and stereotactic fixation.
- Fusion of MRI and CT in the planning system iPlan version 4.1 (BrainLAB AG, Heimstetten, Germany)
- Delineation Gross tumor volume (GTV): metastasis(es) of the brain displayed in the MRI signal in T1 with contrast Clinical target volume (CTV)= GTV Planning target volume (PTV)= CTV with 3 mm margins in all directions
- Physical Planning
- Technique: multiple dynamic arcs, multiple static conformal fields, multiple static modulated fields, multiple static arcs
- isodose prescription: higher isodose that meets the following criteria: Coverage of at least 95% of the PTV with the prescription dose (V100 ≥ 95%) and 95% Of the prescription dose covering at least 99% of the PTV (V95 ≥ 99%).
- Maximum dose allowed in or outside the PTV: 20% of prescription dose, while respecting the tolerance of the organs described below.
- Scores compliance with RTOG
- Dose escalation scheme
Study model It'll be recruited 3 patients to the initial scheme of 4 fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered the study initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with next dose level. The same criteria of recruitment will be performed till any scheme reach the MTD or up to the scheme of 4 fractions of 9 Gy.
- The number of fractions of HSRT will be kept in 4 fractions for all cohorts.
- The initial dose is 5 Gy per day.
- Increasing the dose of one cohort to another will be more than 1 Gy per day of HSRT. For example: If the scheme of 4 fractions of 5 Gy will not have unacceptable toxicity, the study continues to recruit patients for the scheme of 4 fractions of 6 Gy, and so subsequently.
- The study will recruit patients to the fractionation scheme up to four fractions of 9 Gy according to the BEDGy3 be similar to a maximum dose of RS studies to brain metastasis of 24 Gy in one fraction.
- At the discretion of the responsible investigator for the safety of the study, the number of patients may be increased in each cohort during the study.
- Restrictions of radiation dose on critical organ
- optic chiasm: BEDGy3: 90 Gy
- optic nerves: BEDGy3: 90 Gy
- optic tract: BEDGy3: 90 Gy
- brainstem: BEDGy3: 110 Gy
- retina: BEDGy3: 72 Gy
- lens: BEDGy3: 16.7 Gy
- Simulation of HSRT
- Ten days post-WBRT(or next business day, if the date coincides with a weekend or holiday)
- Tests of collision safety and quality control testing to ensure the alignment of isocenters radiation, mechanical and coincidence of lasers (Winston-Lutz test).
- Treatment of HSRT
- Eleventh day post-WBRT(or next business day, if the date coincides with a weekend or holiday)
- Treatment equipment
- linear accelerator of 6-MeV photons (Varian Clinac linear accelerator 600 CD, Varian Medical Systems, Palo Alto, CA, USA)
- Micromultileaf m3 System(BrainLAB AG, Heimstetten, Germany).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSRT - 4fx x 5 Gy | Experimental | Radiation: 4fx x 5GyIt'll be recruited 3 patients to the initial regimen of four fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered that the study was initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with the next dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with 1-3 brain metastases with histological diagnosis of malignancy and ineligible for surgery or RS
- Age ≥18 years
- Karnofsky Performance Status (KPS) ≥ 70%
- "Status" of neurological function: zero to 3
- Anticipated survival > 3 months
Key exclusion criteria (9 listed)
- Prior brain irradiation for any reason
- Indian race
- Primary tumor of lymphoma, leukemia, germ cell, small cell carcinoma or central nervous system
- Leptomeningeal dissemination
- single or multiple metastases with surgical (patients with KPS ≥ 70, with metastatic site in an area not eloquent or herniation causing mass effect or hydrocephalus) or RS indication(patients with KPS ≥ 70 and metastatic lesion <4 cm in diameter with distance to chiasm, tract and optic nerves, and brain stem > 5 mm)
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 |
|---|---|---|
| 4fx x 5GyAlso: hypofractionated stereotactic radiotherapyIt'll be recruited 3 patients to the initial scheme of 4 fractions of 5 Gy on each brain metastasis with HSRT and if no patient has unacceptable toxicity, more 3 patients for subsequent scheme will be recruited. If 2 patients had unacceptable toxicity, the study ends and it'll be considered the study initiated with toxic regimen. If 1 patient has unacceptable toxicity, it'll be recruited 3 more patients for this scheme and if 1 or more patients had unacceptable toxicity, the scheme will be considered toxic and the study will be closed. If no patient develops unacceptable toxicity, the study will follow to the next cohort of 3 more patients with next dose level. The same criteria of recruitment will be performed till any scheme reach the MTD or up to the scheme of 4 fractions of 9 Gy. | Radiation | HSRT - 4fx x 5 Gy |
Primary outcome
Maximum Tolerance Dose
Time frame: Always after 3 patients recruited (up to 30 days after completion of radiotherapy planned)
To establish the MTD with HSRT as a way to increase the dose of radiation after the WBRT for patients with 1-3 brain metastases not eligible for surgery or RS, and find the dose for phase II study.
2 secondary outcomes
Radiotoxicity
Time frame: Up to 30 days after the end of radiotherapy
Neurocognitive benefit
Time frame: Baseline and up to 30 days after completion of radiotherapy planned
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2014.
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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.
Ricardo A Nakamura, MD principal investigator
Barretos Cancer 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 4fx x 5Gy in people with Brain Metastases, run by Barretos Cancer Hospital at 1 site in Brazil.
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 6 inclusion and 9 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: withdrawn, as of the sponsor's last update on 7 Mar 2014. 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 Brazil. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Maximum Tolerance Dose (time frame: Always after 3 patients recruited (up to 30 days after completion of radiotherapy planned)). 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 7 Mar 2014.