A Study to Assess the Efficacy of Cerebellar IMRT Combined With Cerebral SRS in Patients With Brain Metastases

July 25, 2022 updated by: Meirrovitz Amichay, Hadassah Medical Organization

A Single-arm Pilot Study, to Assess the Efficacy of Cerebellar IMRT Combined With Cerebral SRS in Patients With Brain Metastases That Are Predominantly in the Posterior Fossa - a Novel Treatment Approach

A single-arm pilot study, to assess the efficacy of cerebellar IMRT combined with cerebral SRS in patients with brain metastases that are predominantly in the posterior fossa - a novel treatment approach

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study includes patients with brain metastases, presenting with more than 5 cerebellar lesions and less than 10 cerebral lesions. This is a pilot study assessing the efficacy of a novel, combined treatment approach involving Intensity-modulated Radiation Therapy (IMRT)/ Volumetric Modulated Arc Therapy (VMAT), with or without integrated boost to metastases, administered to the posterior fossa, and Stereotactic Radiosurgery (SRS) administered to cerebral lesions. This is opposed to the current recommended treatment approach for such cases, being whole brain radiotherapy (WBRT). While an effective treatment with respect to lesion control, WBRT is not ideal as the total deliverable dose is limited to 30 Gy due to toxicity. In addition, this technique is responsible for major side effects, especially neurocognitive deterioration.

There are select cases of multiple brain metastases which are predominantly found in the posterior fossa. Rectal cancer is one such notorious example, however this type of spread is not limited to one region.

The investigators hypothesize that utilizing the novel combinational treatment approach of IMRT and SRS in cerebral and cerebellar brain metastases will improve long term brain control, maintain the patients' cognitive function and potentially improve overall survival, as the need for potent WBRT will become obsolete.

Patients with multiple brain metastases present in the cerebrum and cerebellum will be treated with SRS and IMRT respectively, simultaneously (within 3 weeks of one another). Brain MRI scans will be performed before commencement of the novel treatment approach, at two month after RT, and then every 3 months, or as indicated clinically, after treatment start. Concurrently at each MRI scan time point, patients will be assessed based on brain and whole-body metastatic progression by RECIST. Patients will also be assessed for central nervous system (CNS) - progression free survival (PFS) and body-PFS, cognitive function, quality of life and overall survival status via standardized follow-up tests.

Study Type

Interventional

Enrollment (Anticipated)

37

Phase

  • Not Applicable

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

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

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. Presence of multiple brain metastasis, predominantly in the posterior fossa: more than 5 metastases in the cerebellum, and less than 10 metastases in the cerebrum, visible on MRI, regardless of tumor origin.
  2. Provided written informed consent.
  3. Be male or female and at least 18 years of age on the day of signing informed consent.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  5. A minimum life expectancy of at least 3 months

  6. Female patients:

    1. Willing to use adequate contraceptive measures until 6 weeks after the final dose of study treatment
    2. Not breast feeding
    3. Have a negative pregnancy test prior to the start of dosing if of childbearing potential or have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
    4. i. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  7. Male patients who are willing to use barrier contraception (i.e. condoms) until 4 months after the final dose of study treatment.

Exclusion criteria

  1. Prior treatment with Whole brain radiation (WBRT) (previous SRS is allowed for limited, up to 4 metastases, six month or more prior to the study treatment, and the index metastases should be all new)
  2. An investigational drug within five half-lives of the compound.
  3. Spinal cord compression unless asymptomatic and stable.
  4. Leptomeningeal disease.

  5. Moderate or severe symptomatic brain metastases defined as per Radiation therapy Oncology Group acute morbidity grade 3 to 4.

    Note: Grade 3 refers to neurological findings requiring hospitalization for initial management. Grade 4 refers to serious neurological impairment including paralysis, coma or seizures more than three times per week despite medication and requires hospitalization.

  6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  7. Involvement in the planning and conduct of the study
  8. Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

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
Intervention / Treatment
Experimental: Treatment
Intensity-modulated Radiation Therapy (IMRT)/VMAT with integrated boost to the cerebellum and metastases and Stereotactic Radiosurgery (SRS) to the cerebral metastases as a novel treatment combination for brain metastases
Radiation: Radiation treatment
Radiation treatment of IMRT to the cerebellum and SRS to the cerebrum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain control: Central Nervous System (CNS)- Progression Free Survival (PFS)
Time Frame: Change in lesion size in the whole body will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month until the date of first documented progression or date of death from any cause, up to 10 years.
Metastatic brain lesions treated with IMRT/SRS will be tracked and measured using MRI. Disease in the brain and systemically will be assessed by RECIST.
Change in lesion size in the whole body will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month until the date of first documented progression or date of death from any cause, up to 10 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive function
Time Frame: Change in patient cognitive function will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month, until the date of first documented progression or date of death from any cause, up to 10 years.
Patient cognitive function will improve after study treatment (Hopkines verbal learning test (HVLT), Trail Making Test (TMT) A + B, Controlled Oral Word Association Test (COWAT) and clock drawing test). Cognitive functions will be univariately compared between the groups using the Student's t-test or the Mann-Whitney Ranks test. We will also perform multivariate analyses using either linear regression of Poisson regression, depending on the outcomes distribution.
Change in patient cognitive function will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month, until the date of first documented progression or date of death from any cause, up to 10 years.
Quality of life (QOL)
Time Frame: Change in patient QOL will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month, until the date of first documented progression or date of death from any cause, up to 10 years.
Patient QOL will improve after study treatment. QOL will be evaluated due to score in four questionnaires: European Organisation for. Research and Treatment of Cancer (EORTC) QLQ C30, The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT), The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS). Cognitive functions will be univariately compared between the groups using the Student's t-test or the Mann-Whitney Ranks test. We will also perform multivariate analyses using either linear regression of Poisson regression, depending on the outcomes distribution.
Change in patient QOL will be followed and assessed at screen, 2 month after radiation treatment, then every 3 month, until the date of first documented progression or date of death from any cause, up to 10 years.
Overall survival (OS)
Time Frame: Status will be checked at every visit and follow up, until the date of death from any cause, up to 10 years.
Patient OS will be assessed via timely patient follow-ups on survival status
Status will be checked at every visit and follow up, until the date of death from any cause, up to 10 years.

Collaborators and Investigators

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

Sponsor

Hadassah Medical Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 (Actual)

February 11, 2021

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

December 12, 2021

First Submitted That Met QC Criteria

July 25, 2022

First Posted (Actual)

July 28, 2022

Study Record Updates

Last Update Posted (Actual)

July 28, 2022

Last Update Submitted That Met QC Criteria

July 25, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0930-20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

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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