Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases
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|ClinicalTrials.gov Identifier: NCT02490878|
Recruitment Status : Terminated (Slow accrual)
First Posted : July 7, 2015
Results First Posted : August 6, 2021
Last Update Posted : August 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Radionecrosis Brain Metastases||Drug: bevacizumab Drug: corticosteroids Other: placebo||Phase 2|
This is a randomized double-blinded phase II study of corticosteroids with bevacizumab vs. corticosteroids with placebo for brain radionecrosis following radiosurgery for brain metastases. This is a two-arm clinical trial with parallel group design for longitudinal quality of life endpoint. Patients will be stratified according to age (≤ 65 years vs. > 65 years), pathological confirmation of necrosis (yes vs. no), MDASI-BT mean global score (symptom + interference scores) ( < 4.0 vs. > 4.0) and prior whole brain radiotherapy (yes vs. no). The primary and secondary objectives are detailed below.
To investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms (clinical and patient-reported symptom improvement associated with radionecrosis and less radionecrosis treatment-induced symptoms) compared with standard corticosteroid therapy.
- To evaluate the toxicity profile associated with bevacizumab and corticosteroid therapy.
- To compare self-reported health related quality of life (HRQOL) using LASA, Dexamethasone Symptoms Questionnaire-Chronic (DSQ-C), and MDASI-BT symptom and interference score between treatment arms.
- To compare intracranial progression-free survival and time to maximum radiographic response between treatment arms.
- To compare the dose and duration of corticosteroids required between treatment arms and correlate steroid requirement with DSQ-C and MDASI-BT scores.
Patient event monitoring will occur every 2 months after treatment up to 6 months. Then event monitoring will occur up to one year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Supportive Care|
|Official Title:||Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases|
|Actual Study Start Date :||April 2016|
|Actual Primary Completion Date :||February 1, 2019|
|Actual Study Completion Date :||April 25, 2020|
Experimental: bevacizumab + corticosteroids
The patient will receive bevacizumab 10 mg/kg IV given on days 1 and 15 of a 28 day cycle for 4 cycles. Once the patient has started the study treatment, the dose of corticosteroids will be tapered every 5 days (e.g., dexamethasone 2 mg or prednisone 15 mg per taper), as tolerated, under the management of the treating MD. If patients deteriorate while tapering, dexamethasone will be increased up to a maximum of 16 mg per day, as per treating MD, to manage symptoms.
Patients who meet the criteria for clinical progression will be treated as per treating MD.
Experimental: placebo + corticosteroids
The patient will receive placebo 0.9% NaCl volume equal to bevacizumab volume added to 100 mL bag of 0.9% NaCl delivered IV given on days 1 and 15 of a 28-day cycle for 4 cycles. Once the patient has started the study treatment, the dose of corticosteroids will be tapered every 5 days (e.g., dexamethasone 2 mg or prednisone 15 mg per taper), as tolerated, under the management of the treating MD. If patients deteriorate while tapering, dexamethasone will be increased up to a maximum of 16 mg per day, as per treating MD, to manage symptoms.
Patients who meet the criteria for clinical progression will be allowed to receive bevacizumab according to the protocol.
- Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score [ Time Frame: Baseline, 2, 4, 6 and 8 weeks ]The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Symptom Severity) is the average of the subscale items with 0 being "not present" and 10 being "as bad as you can imagine.", given that a specified minimum numbers of items were completed. A negative change in score from baseline to given time point indicates a worsening score.
- Toxicity (CTCAE Version 4.0) [ Time Frame: Up to 1.5 years post-treatment ]Toxicity associated with bevacizumab and corticosteroids in patients with radionecrosis using CTCAE Version 4.0. The number of patients reporting a grade 3 or higher, 4 or higher, or 5 at least possibly related to treatment are included in this table.
- Quality of Life Measure Using the Single Item Linear Analogue Scale (LASA) [ Time Frame: Up to 1.5 years post-treatment ]The Linear Analogue Scale used is a 5-question survey. Patients are asked to score the following questions on a 1(as bad as it can be) -10 (as good as it can be) scale: 1) your overall quality of life, 2) your overall (intellectual) well being, 3) your overall physical well being, 4) your overall emotional well being, and 5) your overall spiritual well being. The change in score was computed from baseline to 1.5 years post-treatment. A negative difference is thought of as a worsening score from baseline.
- Quality of Life Measure Using the Dexamethasone Symptoms Questionnaire - Chronic (DSQ-C) [ Time Frame: Baseline and weeks 2, 4, 6, 8 of treatment ]The DSQ-C was developed for use in the brain tumor patient population. It consists of 18 questions rated on a 4-point scale (1 to 4, with 4 indicating a worse symptom) to indicate the presence and severity of symptoms. For each patient, the sum across all 18 questions were computed(18-72, with 18 being a score of 1 for each of the 18 questions and 72 being a score of 4 for each of the questions, refering to the previous sentence, a score of 18(a score of 1, 18 times) indicates the best possible score. A score of 72(a score of 4, 18 times) indicates the worst possible. The mean for total score across each week (weeks 2, 4, 6, 8) is reported.
- Quality of Life Measure Using the The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Score. [ Time Frame: Up to 1.5 years post-treatment ]The MDASI-BT was developed and validated for use in the brain tumor patient population, including those with brain metastases and typically requires less than 4 minutes to complete. It consists of 23 symptoms rated on a 0 to 10 numerical rating scale (NRS) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." MDASI-BT Symptom Scoring: A global symptom score for the MDASI symptom severity scale is obtained by taking the average of the 23 items together. This puts the score on a 0-10 scalenumerical rating scale (NRS) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." The mean global symptom at baseline and at weeks 2, 4, 6, 8 were used in this analysis.
- Progression Free Survival [ Time Frame: Up to 16 weeks ]Progression free survival is defined as the time from start of treatment to the earliest of the date patient stops placebo or bevacizumab for either alternative therapy or crossover to bevacizumab (if initially on placebo). Result will be summarized by Kaplan-Meier method.
- Time to Maximum Radiographic Response [ Time Frame: Up to 16 weeks ]Time from start of treatment to maximum radiographic response
- Time to Stopping Corticosteroids [ Time Frame: Up to 16 weeks ]Time to stopping corticosteroids is defined as the time from start of protocol treatment to the last day corticosteroids were given. Time to stopping corticosteroid will be summarized by Kaplan-Meier curve with log-rank tests conducted to investigate differences between treatment arms.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02490878
|Study Chair:||Caroline Chung, MD||M.D. Anderson Cancer Center|