Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of the Efficacy of Hippocampal Avoidance on the Cognitive Toxicity of Whole-Brain Radiation Therapy After Surgical Resection of Single Brain Metastasis of Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01942980
Recruitment Status : Completed
First Posted : September 16, 2013
Last Update Posted : August 13, 2018
Sponsor:
Information provided by (Responsible Party):
Institut Paoli-Calmettes

Brief Summary:

The incidence of brain metastases (BM) in metastatic breast cancer is increasing, due to the improvement in the control of systemic disease, and due to an improved detection through imagery.

The treatment management of single BM remains controversial. Indeed, even though it is widely accepted that local treatment increases the median survival time in patients having a good prognostic status, the adding of "adjuvant" whole-brain radiation therapy (WBRT) is currently subject to controversy, due to its potential toxicity. Yet, two randomized trials have demonstrated a clear increase in intra-cerebral recurrence and in death from neurologic origin in case of absence of "adjuvant" WBRT, without change in overall survival (but overall survival was not a primary endpoint in any of these studies).

The data from literature on cognitive toxicity (CT) of WBRT on BM are scarce and sometimes controversial. CT of WBRT affects the subcortical frontal functions. It is postulated that the alteration of hippocampal neurogenesis (mainly due to inflammation process), situated in the subgranular zone of the dentate gyrus, has an essential role in the development of these brain dysfunctions.

It has been shown that the incidence of BM in the hippocampal region (hippocampus + 5mm expansion) is low, in the range of 8,6%.

New irradiation techniques, in particular intensity-modulated radiotherapy associated with rotational radiotherapy, allow to modulate the dose on an intra-cerebral structure, all the while distributing an adapted dose to the remaining brain.

This prospective, randomized study, will compare, through a battery of neuropsychological tests, the cognitive impact of WBRT of 40 Gy in 20 fractions with or without hippocampal avoidance by intensity modulated radiotherapy, in patients presenting with a single operated brain metastasis of breast cancer. If the hippocampal avoidance leads to a significant improvement in cognitive function, this radiotherapy scheme could become the standard postoperative treatment to be proposed to patients presenting the best prognostic factors. This would allow to prevent long-term cognitive deficit, while preserving WBRT benefit on intra-cerebral control.

Justification of evaluation criteria :

Principal criteria :

Evaluation criteria to assess cognitive toxicity have been selected on the basis of the recommendations from C. Meyers and P. Brown, who propose an adapted test battery to evaluate memory, verbal function, visual and motor coordination, and executive function. The selected tests have been validated, also in French. They comprise HVLT-R (Hopkins Verbal Learning Test Revised), COWAT (Controlled Oral Word Association Test), Grooved Pegboard test, TMT A and B (Trailmaking tests A and B), and MMSE. The calculation of patient numbers was based on the HVLT-R test, as memory is thought to be the most frequently affected domain.

The tests will be performed before treatment ("baseline" cognitive function), at 4 months and at 12 months. In case of a missing answer to the evaluation tests, the reason(s) for not answering will be noted.

Secondary criteria :

Quality of life : QLQ-C30, QLQ-BN20, ADL, IADL Intra-cerebral Progression-free survival (PFS) Overall survival.


Condition or disease Intervention/treatment Phase
Breast Cancer Brain Metastasis Radiation: Radiation therapy Brain metastasis in breast cancer Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind Randomized Multicenter Phase III Study Evaluation of the Efficacy of Hippocampal Avoidance on the Cognitive Toxicity of Whole-brain Radiation Therapy After Surgical Resection of Single Brain Metastasis of Breast Cancer.
Study Start Date : March 2013
Actual Primary Completion Date : March 22, 2016
Actual Study Completion Date : June 6, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
conventional postoperative whole-brain radiation therapy
conventional postoperative whole-brain radiation therapy (40 Gy in 20 fractions of 2 Gy)
Radiation: Radiation therapy Brain metastasis in breast cancer
Radiation

whole-brain radiation therapy with hippocampal avoidance
Radiation therapy with hippocampal avoidance
Radiation: Radiation therapy Brain metastasis in breast cancer
Radiation




Primary Outcome Measures :
  1. To assess cognitive toxicity [ Time Frame: From inclusion/randomization to 12 months ]
    Evaluation criteria to assess cognitive toxicity have been selected on the basis of the recommendations from C. Meyers and P. Brown, who propose an adapted test battery to evaluate memory, verbal function, visual and motor coordination, and executive function. The selected tests have been validated, also in French. They comprise HVLT-R (Hopkins Verbal Learning Test Revised), COWAT (Controlled Oral Word Association Test), Grooved Pegboard test, TMT A and B (Trailmaking tests A and B), and MMSE. The calculation of patient numbers was based on the HVLT-R test, as memory is thought to be the most frequently affected domain.


Secondary Outcome Measures :
  1. Quality of life [ Time Frame: At inclusion/randomization, at month 1, month 4 and month 12 ]
    Quality of life : QLQ-C30, QLQ-BN20, ADL, IADL. Intra-cerebral Progression-free survival (PFS) up to 24 months. Overall survival up to 24 months.

  2. Intra-cerebral progression [ Time Frame: Evaluated every 3 months ]
    to assess by RMI or clinical signs

  3. Overall survival [ Time Frame: up to 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > or equal 18 years old,
  • Single brain metastasis from breast cancer, first cerebral event,
  • Complete surgical resection of cerebral metastasis,
  • Histological confirmation of brain metastasis of breast cancer,
  • Start of radiotherapy within 6 weeks after surgery,
  • Karnofsky > or equal to 70,
  • No history of brain radiotherapy,
  • Signed informed consent to participate,
  • Patient affiliated to a social security system or benefiting from such a system.

Exclusion Criteria:

  • Multiple brain metastases, leptomeningeal metastases,
  • macroscopic metastasis surgery not complete,
  • Warning signs of brain displacement (uncontrolled oedema),
  • History of cerebral irradiation or absence of surgical treatment of the current metastasis,
  • History of cancer in the previous 5 years prior to entry in the study, other than cutaneous basal cell carcinoma or in situ epithelioma of uterine cervix or the stated breast cancer,
  • MMSE (Mini Mental State Examination)< 24,
  • all previous systemic treatments less than 2 weeks are not allowed,
  • Pregnant women or liable to become pregnant, lactating women,
  • Persons deprived of their freedom or under tutelage
  • Patients unable to comply with medical procedures of the study for geographical, social, or psychological reasons.

Information from the National Library of Medicine

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): NCT01942980


Locations
Layout table for location information
France
Agnès TALLET
Marseille, France, 13009
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
Layout table for investigator information
Principal Investigator: Agnès TALLET, MD Institut Paoli-Calmettes

Additional Information:
Layout table for additonal information
Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT01942980     History of Changes
Other Study ID Numbers: PHIToN / IPC 2012-005
First Posted: September 16, 2013    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018

Keywords provided by Institut Paoli-Calmettes:
Breast cancer
one brain metastasis

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases