Chemotherapy-Induced Cognitive Impairment in Ovarian Cancer Patients

Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a spectrum
of neurocognitive deficits experienced during and after the administration of chemotherapy
for cancer. The incidence of CICI is significant, affecting anywhere from 25 to 75% of
survivors, and the biologic basis is unknown. This novel study is designed to address the
questions of incidence and biological cause for CICI, while gaining a better understanding of
the structural and functional effects of chemotherapy on the brain. In order to address these
important objectives, a diverse team of experienced investigators has been assembled to
design and implement the proposed protocol. The research team for this project seeks to
accomplish the proposed objectives through following mechanisms: 1) assessment of the
neurocognitive domains affected in CICI using a tailored battery of cognitive tests to define
CICI; 2) measurement of serum markers of oxidative stress and correlation of these markers
with neurocognitive test results; and 3) exploration of structural and functional changes in
the brain during cognitive tasks and correlation of results with markers of oxidative stress
and neurocognitive test results.

Inclusion Criteria:

1. Patients with any stage epithelial ovarian cancer, including cancers arising from the
fallopian tube and primary peritoneal cancer, or patients with other gynecologic
malignancy (any stage), who are chemotherapy-naïve, and scheduled to undergo at least
6 cycles of intravenous platinum/taxane-based chemotherapy.

2. Patients must have adequate bone marrow, renal, hepatic, and sensory neurologic
function to be eligible to receive platinum/taxane-based chemotherapy.

3. Patients must have a World Health Organization Performance Status of ≤ 2.

4. Age ≥18 years.

5. Ability to understand and the willingness to sign an approved written informed consent
document.

Exclusion Criteria:

1. Patients who have received prior cytotoxic chemotherapy are ineligible. Patients may
have received prior adjuvant hormonal therapy for localized breast cancer, provided
that it was completed prior to registration, and that the patient remains free of
recurrent or metastatic disease.

2. Patients undergoing neoadjuvant chemotherapy with planned interval cytoreductive
surgery and adjuvant therapy are not included in this group.

3. Patients who are receiving any other investigational agents are excluded.

4. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic outcomes and other
adverse events.

5. With the exception of non-melanoma skin cancer and other specific malignancies noted
above, patients with other invasive malignancies who had (or have) any evidence of the
other cancer present within the last five years or whose previous cancer treatment
contraindicates this therapy are excluded.

6. Patients with underlying dementia (or on medications to treat Alzheimer's disease such
as donepezil, rivastigmine, galantamine, tacrine, or memantine), encephalopathy, or
other neurological disorder known to adversely affect cognition (such as epilepsy or
prior stroke) are excluded. (Patients with depression or anxiety are not excluded).

7. Patients will be excluded from fMRI testing if they are left-handed, claustrophobic,
have a pacemaker, or have metal implants. Patients not undergoing fMRI testing may
still enroll in clinical trial, including the ERP testing, if all other eligibility
criteria are met.

8. Patients who are pregnant or nursing are excluded. Pregnant women are excluded from
this study because cytotoxic chemotherapy has the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with cytotoxic
chemotherapy, breastfeeding should be discontinued if the mother is treated with
cytotoxic chemotherapy.

9. Patients who are non-English speaking are excluded because of the inability to
adequately administer neurocognitive testing in non-English languages.