Phase I Dose Escalation in Patients With 1-3 Unresectable Brain Metastases

March 5, 2014 updated by: Barretos Cancer Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil, 14784-400
        • Barretos Cancer Hospital - Fundação Pio XII

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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..

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: HSRT - 4fx x 5 Gy
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.
Radiation: 4fx x 5Gy
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.
Other Names:
  • hypofractionated stereotactic radiotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Always after 3 patients recruited (up to 30 days after completion of radiotherapy planned)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Radiotoxicity
Time Frame: Up to 30 days after the end of radiotherapy
CTCAE version 3.0
Up to 30 days after the end of radiotherapy
Neurocognitive benefit
Time Frame: Baseline and up to 30 days after completion of radiotherapy planned
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).
Baseline and up to 30 days after completion of radiotherapy planned

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Barretos Cancer Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ricardo A Nakamura, MD, Barretos Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 7, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HSRT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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