Clinical trial NCT00755313: Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer
Official title: Effects of Chemotherapy on Brain Structure and Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Chemotherapeutic Agent Toxicity
Cognitive/Functional Effects
Fatigue
Long-term Effects Secondary to Cancer Therapy in Adults
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Keywords: cognitive/functional effects
fatigue
long-term effects secondary to cancer therapy in adults
psychosocial effects of cancer and its treatment
chemotherapeutic agent toxicity
neurotoxicity
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
estrogen receptor-negative breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-negative breast cancer
progesterone receptor-positive breast cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-09-18
Enrollment: 81
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: women with newly diagnosed, early stage breast cancer

Brief summary: RATIONALE: Gathering information over time from laboratory tests, imaging scans, and assessment tests may help doctors learn more about the side effects of chemotherapy and plan the best treatment.

PURPOSE: This clinical trial is studying the effects of chemotherapy on the brain in women with newly diagnosed early-stage breast cancer.

Detailed description: OBJECTIVES:

Primary

* To prospectively evaluate the acute (1 month after chemotherapy) and relatively long-term (18 months after chemotherapy) effects of standard-dose chemotherapy and/or hormonal therapy with aromatase inhibition on brain function using positron emission tomography (PET) and the glucose metabolism tracer fludeoxyglucose F 18 in women with newly diagnosed, early stage breast cancer.

Secondary

* To evaluate the acute and relatively long-term effects of chemotherapy and/or hormonal therapy on MRI measurements of hippocampal volume, cortical grey matter volume, white matter signal hyperintensities, ventricular volume, and whole brain volume in these patients.
* To evaluate the acute and relatively long-term effects of chemotherapy and/or hormonal therapy with aromatase inhibition on cognitive function in these patients.
* To explore the characteristics of these patients that renders them more vulnerable to chemotherapy and/or estrogen suppression-induced cognitive decline.

OUTLINE: Patients are stratified according to planned adjuvant chemotherapy (chemotherapy and hormonal therapy vs hormonal therapy vs chemotherapy vs no therapy) and the hormone receptor status (positive vs negative).

Patients (groups A-C) undergo bioavailable estradiol measurements, PET scans, and MRI scans at baseline and 1 and 18 months after treatment. Patients also undergo cognitive, neuropsychological, sociodemographic, and quality of life assessments using a battery of study tests and questionnaires at baseline and at 1, 9, and 18 months after treatment. Group D participants (controls) undergo the same testing at equivalent intervals.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of breast cancer, meeting 1 of the following criteria:

  * Group A

    * Stage I, II, or III invasive disease
    * Hormone receptor-positive disease
    * Planned adjuvant chemotherapy including an anthracycline and taxane using either dose-dense or docetaxel, doxorubicin hydrochloride, and cyclophosphamide (TAC) regimens with or without trastuzumab (Herceptin®) for 4 months; docetaxel and cyclophosphamide (TC) with or without trastuzumab for 3 months; doxorubicin hydrochloride and cyclophosphamide (AC) for 3 months; or doxorubicin hydrochloride, carboplatin, and trastuzumab (TCH) for 4 months (trastuzumab may be given for 1 year and is not considered chemotherapy for the purpose of this study)
    * Planned treatment with adjuvant aromatase inhibitors (AI) for 5 years
  * Group B

    * Stage I or II invasive disease
    * Planned treatment with adjuvant AI with or without radiotherapy
  * Group C

    * Stage I, II, or III disease
    * Hormone-receptor negative
    * Planned adjuvant chemotherapy as in group A
    * No treatment with AI planned
  * Group D

    * Healthy controls free of any major medical or psychiatric disorders
    * Not taking prescription medications, including hormone-replacement therapy, or other substances that might influence performance on neuropsychological tests
    * Balanced with the patient groups on age, education, ethnicity, and sociodemographic background

PATIENT CHARACTERISTICS:

* No history of psychiatric illness other than minor depression
* No history of psychiatric illness other than minor depression in immediate family members
* No history of neurologic disease
* No history of drug or alcohol abuse
* No significant medical illness other than breast cancer
* No heart pacemaker or metallic implants or particles in the body
* No heart rhythm disturbance
* No claustrophobia
* No prior serious head injury
* No tattoos or permanent cosmetics
* No unremovable body jewelry
* No cognitive impairment
* Able to read and speak English
* No condition that compromises compliance with the objectives and procedures of this study, as judged by the principal investigator

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy, CNS radiotherapy, or intrathecal therapy
* Premenopausal women receiving aromatase inhibitors must also be receiving ovarian suppression
* No concurrent narcotics or major antipsychotic medications that may impair cognition

Primary outcomes:
measure: Change in glucose metabolism
timeFrame: Up to 18 months after treatment
Secondary outcomes:
measure: MRI measures of the brain (hippocampal volume, cortical gray matter volume, white matter signal hyperintensities, ventricular volume, whole brain volume)
timeFrame: Up to 18 months after treatment
measure: Measures of cognitive function over time by Wechsler memory scale, word list memory, Stroop Color Word Test, Boston Naming Test, verbal fluency, FACIT-B functional assessment, Mini Mental State Exam, Hamilton Depression Rating Scale (Ham-D), Beck De ...
timeFrame: Up to 18 months after treatment
measure: Cognitive assessments over time by FACIT-B, Ham-D, BDI-II, STAI, FSI, and MASQ, demographic and medical data
timeFrame: Up to 18 months after treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Hope S. Rugo, MD
role: PRINCIPAL_INVESTIGATOR
References: