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Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases

2021. január 5. frissítette: Robert Timmerman, University of Texas Southwestern Medical Center

Phase II Trial of Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases

The investigators hypothesize that avoidance of the hippocampal region with WBRT (Whole-Brain Radiotherapy ) may delay or reduce the onset, frequency, and/or severity of NCF (neurocognitive function) decline, as measured with clinical neurocognitive tools.

A tanulmány áttekintése

Állapot

Befejezve

Beavatkozás / kezelés

Részletes leírás

We propose to use conformal avoidance of the hippocampal region during whole brain radiotherapy to reduce the dose to the hippocampi, thereby putatively limiting the radiation-induced inflammation of the hippocampal region and subsequent alteration of the microenvironment of the neural progenitor cells

Tanulmány típusa

Beavatkozó

Beiratkozás (Tényleges)

50

Fázis

  • 2. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi helyek

    • Texas
      • Dallas, Texas, Egyesült Államok, 75390
        • University of Texas Southwestern Medical Center

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

18 év (Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Nem

Tanulmányozható nemek

Összes

Leírás

Inclusion Criteria:

  1. Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy.. Direct biopsy of CNS (central nervous system) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent. Patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy.
  2. Patients with measurable brain metastasis outside a 5-mm margin around either hippocampus
  3. Patients with measurable brain metastasis who have not been or will not be treated with SRS (stereotactic radiosurgery ) or surgical resection (Note: These treatment options are only permitted at relapse)
  4. History/physical examination within 28 days prior to registration
  5. Patients must fall into RTOG (Radiation Therapy Oncology Group) recursive partitioning analysis (RPA) class I or II
  6. Patients must have a life expectancy of at least 4 months.
  7. Age ≥ 18 years
  8. Karnofsky performance status ≥ 70
  9. Patients must provide study-specific informed consent prior to study entry
  10. Women of childbearing potential and male participants must practice adequate contraception
  11. Women of childbearing potential must have a negative, qualitative serum pregnancy test ≤2 weeks prior to study entry

Exclusion Criteria:

  1. Patients with greater than 9 discrete metastases on MRI.
  2. Patients with leptomeningeal metastases
  3. Patients with measurable brain metastasis not resulting from small cell lung cancer and germ cell malignancy
  4. Plan for chemotherapy or targeted therapies during WBRT or over the subsequent 7 days
  5. Contraindication to MR (Magnetic resonance) imaging such as implanted metal devices or foreign bodies, severe claustrophobia AND patients unable to receive gadolinium contrast agents
  6. Serum creatinine > 1.4 mg/dl ≤ 28 days prior to study entry
  7. Prior radiation therapy to the brain
  8. Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesions

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: N/A
  • Beavatkozó modell: Egyetlen csoportos hozzárendelés
  • Maszkolás: Nincs (Open Label)

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Kísérleti: Radiation
Whole-Brain Radiotherapy
Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score
Időkeret: Baseline, 3 months

The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.

*Delayed*recall was measured by recalling the 12 targets after a 20-minute delay.

1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, 3 months

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Mean Change in *Immediate* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Időkeret: Baseline, at 3 months

The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.

*Immediate* recall was measured by memorizing a list of 12 targets for 3 consecutive trials.

1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, at 3 months
Mean Change in *Delayed Recognition* Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Időkeret: Baseline, 3 months

The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.

*Delayed recognition* was measured by using recognition discrimination index.

1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, 3 months
Mean Change in Neurocognitive Function as Measured by Controlled Word Association Test
Időkeret: Baseline, at 3 months

Controlled Word Association Test (COWAT) is used to assess language and executive/frontal skills. The patient produces as many words as possible in 1 min. (each) for a specific letter (C, F, L or P, R, W). Requires about 5 min to complete.

1 point is awarded for each word produced. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, at 3 months
Mean Change in Trail Making Test (TMT- A) Score
Időkeret: Baseline, at 3 months

Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers.

The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B.

In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order.

Possible score ranges from 0-3 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, at 3 months
Mean Change in Trail Making Test (TMT- B) Score
Időkeret: Baseline, at 3 months

Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers.

The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B.

In Part B, the circles include both numbers (1 - 13) and letters (A - L). Possible score ranges from 0-5 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.

Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Medical Outcomes Scale (MOS)
Időkeret: Baseline, at 3 months

Medical Outcomes Scale (MOS) assess cognitive function with possible score range from 0-100, with higher scores indicating better outcome.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Mini-Mental Status Examination (MMSE)
Időkeret: Baseline, at 3 months

Mini-Mental Status Examination (MMSE) is a brief, standardized tool to grade patients' global cognitive function. Possible scores range from 0-30, with lower score indicating severe cognitive impairment.

Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Baseline, at 3 months
Mean Change in Relative Fatigue as Measured by Multidimensional Fatigue Inventory (MFI-20) Scores
Időkeret: Baseline, 3 months
The MFI-20 is a multidimensional, self-reporting instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Possible subscore ranges from 4 to 20 is reported for each dimension, with 20 corresponding to maximal fatigue.
Baseline, 3 months
Cumulative Incidence of Local Failure
Időkeret: 1 year

Cumulative incidence of local failure, defined as tumor recurrence . Percent local failure at 1 year.

The Cox proportional hazards regression model will be used to evaluate Cumulative incidence of local failure.

This is to evaluate local control of brain metastases treated with integrated boost.

1 year
Cumulative Incidence of Intracranial Failure
Időkeret: 1 year

Cumulative incidence of intracranial failure was estimated by the Cox proportional hazards regression model.

Intracranial failure is any failure in the brain.

1 year
Percentage of Participants With Local Failures Within the Region of Brain Within the CTV Receiving 20 Gy
Időkeret: 1 year
Percentage of participants with local failures within the region of brain within the CTV (Clinical Target Volume ) receiving 20 Gy
1 year
Number of Participants With Recurrence in the Hippocampus
Időkeret: 5 months
Recurrence in the hippocampus was noted after hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT)
5 months
Median Progression Free Survival
Időkeret: 39 months
Tumor progression is measured radiographically. The Kaplan-Meier estimator was used to determine the median time to death for this patient population.
39 months
Median Overall Survival.
Időkeret: 39 months
Overall survival is measured by the Kaplan-Meier estimator used to determine the median overall survival for this patient population.
39 months
Number of Adverse Events Grade 3 or Higher Based on CTCAE (Common Terminology Criteria for Adverse Events) Criteria.
Időkeret: From start of treatment up to 39 months
The adverse event (AE) including any adverse event would be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
From start of treatment up to 39 months
Health-related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy With Brain Subscale (FACT-BR)
Időkeret: 39 months

Quality of life will be assessed using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). The FACT-BR is a multidimensional, self-report quality of life instrument specifically designed and validated for use with brain malignancy patients. It is written at the 4th grade reading level and can be completed in 5-10 minutes with little or no assistance in patients who are not neurologically incapacitated. It measures quality of life related to symptoms or problems across 5 scales: physical well-being (7 items); social/family well-being (7 items);emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items).

Items are rated on a 5-point scale (0-5): 0-"not at all", 1- "a little bit", 2-"somewhat", 3-"quite a bit" and 4-"very much", with HIGHER scores indicating a better quality of life.

39 months
Health-related Quality of Life as Assessed by Euroqol EQ-5D
Időkeret: 39 months

The EQ (Euroqol)-5D (5 Dimension) health related quality of life questionnaire is a standardized instrument for use as a measure of health outcome.

Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. . The US version of the EQ-5D will be used, to enable mapping of general HR-QoL (Health-related quality of life) scores from EQ-5D scores into health state utility scores (ranging from 0 to 1) for the US population.

Possible scores range from 0 to 1, with HIGHER scores indicating a better quality of life.

39 months

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Nyomozók

  • Kutatásvezető: Robert Timmerman, MD, UT Southwestern Medical Center Dallas

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete (Tényleges)

2011. október 18.

Elsődleges befejezés (Tényleges)

2019. december 16.

A tanulmány befejezése (Tényleges)

2019. december 16.

Tanulmányi regisztráció dátumai

Először benyújtva

2011. augusztus 10.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2011. augusztus 10.

Első közzététel (Becslés)

2011. augusztus 11.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2021. január 26.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2021. január 5.

Utolsó ellenőrzés

2020. március 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .

Klinikai vizsgálatok a Radiotherapy

3
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