Study of CoQ10 During One Cycle of Doxorubicin Treatment for Breast Cancer

Doxorubicin is a lifesaving breast cancer treatment. However, approximately 3-20% of women
who receive doxorubicin treatment experience some damage to their heart muscle. Coenzyme Q10
is a fat soluble antioxidant dietary supplement that may protect against this heart damage
during doxorubicin treatment. It is unknown how Coenzyme Q10 may interact with doxorubicin.
This study will assess the effects of Coenzyme Q10 on doxorubicin metabolism.

This is a phase I randomized, placebo-controlled, cross-over pharmacokinetic and
dose-finding study to assess the safety of CoQ10 during doxorubicin treatment for breast
cancer. Safety will be assessed by measuring 1) intra-patient differences in doxorubicin and
its active metabolites, with and without CoQ10, and 2) adverse events. We hypothesize that
CoQ10 administration during doxorubicin treatment is safe and will not affect doxorubicin
active metabolites. Using three dose levels of CoQ10, the maximum tolerated dose (MTD) will
be determined by assessing change in doxorubicin concentration (area under the curve (AUC),
change in peak concentration levels (Cmax)), and adverse events.

Inclusion Criteria:

- Diagnosis of early stage breast cancer (stage I, II, or III);

- Scheduled to receive at least four rounds of dose dense doxorubicin therapy in the
neoadjuvant or adjuvant setting;

- No other history of prior chemotherapy, radiation, or hormonal therapy in the
previous 5 years;

- For women receiving adjuvant therapy, single lumen implanted venous access device
(i.e. single port) for unilateral cancer and double lumen implanted venous access
device (i.e. double port) for bilateral breast cancer

- Age 21 years or older;

- ECOG performance status ≤ 2 (Karnofsky > 60%);

- Normal organ and marrow function defined as: Leukocytes ≥ 3,000/uL, Absolute
neutrophils count (ANC) ≥ 1,500/uL at baseline, Platelets ≥ 100,000/uL, Total
bilirubin ≤ 1.5 X normal institutional limits, AST (SGOT)/ALT (SGPT) ≤ 2.5 X
institutional ULN, Serum creatinine within normal institutional limits;

- Left ventricular ejection fraction > 55%;

- No history of CoQ10 supplement use within 30 days of initiating study drug;

- No uncontrolled or significant co-morbid illness;

- Not pregnant, not breastfeeding, and not planning on becoming pregnant during the
course of the study;

- Willingness to comply with all study intervention and follow-up procedures;

- Ability to speak English or Spanish; and

- Ability to provide informed consent.

Exclusion Criteria:

- Inability to understand or an unwillingness to sign a written informed consent
document;

- Any significant toxic side effects related to first or second dose of
doxorubicin/cyclophosphamide chemotherapy or biologic therapy that did not resolve to
less than a CTCAE 3.0 grade 3 non-hematological toxicity;

- Currently using any investigational agent;

- Unstable or severe intercurrent medical condition that, in the opinion of the
investigator, might interfere with the participant's ability to follow the protocol
or achieve study objectives;

- Psychological or sociological conditions, addictive disorders, or family problems
that would preclude adherence with study drug or compliance with the protocol

- Women who report pregnancy, are breast feeding, or have a positive pregnancy test;

- Use of CoQ10 supplement use within 30 days of initiating study drug;

- Use of over-the-counter nutritional vitamin greater than 5x RDA;

- Fish allergy (due to fish-based softgel shell);

- Currently taking FDA cardioprotective drugs, such as Zinecard (dexrazoxane);

- History of chronic hepatitis B, hepatitis C, and HIV infection;

- Problems swallowing oral medications due to prolonged emesis, mucositis, esophageal
dysfunction, etc.; and,

- Currently taking any form of antioxidant supplements while on study.

- Use of warfarin.

- Kosher (due to fish-based softgel shell)

- Dietary restriction of tilapia (due to tilapia fish-based softgel shell)

- Titanium Dioxide allergy (due to the opaque coloring used in the softgel).