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

Sponsor

Heather Greenlee (Other)

Overall Status

Unknown status

CT.gov ID

NCT00976131

Collaborator

National Institutes of Health (NIH) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study hopes to examine the effects of Coenzyme Q10 on doxorubicin (Adriamycin) metabolism during breast cancer treatment.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Coenzyme Q10 Other: Coenzyme Q10 Placebo	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Phase I Randomized, Placebo-Controlled, Cross-Over, Dose-Finding Pharmacokinetic Study of CoQ10 During One Cycle of Doxorubicin Treatment for Breast Cancer

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Sep 1, 2012

Anticipated Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Arm A Cycle 3 of doxorubicin with Coenzyme Q10, Cycle 4 with Coenzyme Q10 Placebo	Drug: Coenzyme Q10 Dose Level 1: 300mg/d (2 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 300mg/d placebo (2 capsules)taken daily for two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 2: 600mg/d (4 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 600mg/d placebo (4 capsules) taken daily for two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 3: 1200mg/d (8 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 1200mg/d placebo (8 capsules) taken daily for two weeks prior to Cycle 4 infusion of doxorubicin. Other Names: CoQ10
Experimental: Arm B Cycle 3 of doxorubicin with Coenzyme Q10 Placebo, Cycle 4 with Coenzyme Q10	Other: Coenzyme Q10 Placebo Dose Level 1: 300mg/d placebo (2 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 300mg/d (2 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 2: 600mg/d placebo (4 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 600mg/d (4 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 3: 1200mg/d placebo (8 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 1200mg/d (8 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin.

Arm

Intervention/Treatment

Placebo Comparator: Arm A

Cycle 3 of doxorubicin with Coenzyme Q10, Cycle 4 with Coenzyme Q10 Placebo

Drug: Coenzyme Q10

Dose Level 1: 300mg/d (2 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 300mg/d placebo (2 capsules)taken daily for two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 2: 600mg/d (4 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 600mg/d placebo (4 capsules) taken daily for two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 3: 1200mg/d (8 capsules) of CoQ10 taken daily for two weeks prior to Cycle 3 infusion of doxorubicin followed by 1200mg/d placebo (8 capsules) taken daily for two weeks prior to Cycle 4 infusion of doxorubicin.

Other Names:

CoQ10

Experimental: Arm B

Cycle 3 of doxorubicin with Coenzyme Q10 Placebo, Cycle 4 with Coenzyme Q10

Other: Coenzyme Q10 Placebo

Dose Level 1: 300mg/d placebo (2 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 300mg/d (2 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 2: 600mg/d placebo (4 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 600mg/d (4 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin. Dose Level 3: 1200mg/d placebo (8 capsules) taken daily two weeks prior to Cycle 3 infusion of doxorubicin followed by 1200mg/d (8 capsules) of CoQ10 taken daily two weeks prior to Cycle 4 infusion of doxorubicin.

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of CoQ10 that does not alter the pharmacokinetics of doxorubicin [Two weeks prior to cycles 3 and 4 of doxorubicin]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).