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

NCT ID: NCT00976131

Last Updated: 2022-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2021-01-20

Brief Summary

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

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. The investigator hypothesizes 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Arm A Placebo

Patients will begin taking their study pills (CoQ10) on the morning of Cycle 2 Day 3 (11-15 days prior to Cycle 3), and will continue taking the study pills through the morning of their Cycle 3 infusion (Day 1 Cycle 3). Patients will then be crossed-over to the alternative condition. On the morning of Cycle 3 Day 3, patients will begin taking their study pills (CoQ10 placebo) and will continue taking the study pills through the morning of their Cycle 4 infusion (Day 1 Cycle 4).

Infusion will be standard of care chemotherapy with doxorubicin and cyclophosphamide.

Group Type: PLACEBO_COMPARATOR

CoQ10

Intervention Type: DRUG

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d CoQ10 (2 capsules) Dose Level 2: 600mg/d CoQ10 (4 capsules) Dose Level 3: 1200mg/d CoQ10 (8 capsules)

CoQ10 Placebo

Intervention Type: OTHER

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d placebo (2 capsules) Dose Level 2: 600mg/d placebo (4 capsules) Dose Level 3: 1200mg/d placebo (8 capsules)

Doxorubicin

Intervention Type: DRUG

Standard of care chemotherapy medication used to treat cancer.

Cyclophosphamide

Intervention Type: DRUG

Standard of care chemotherapy medication used to treat cancer.

Arm B CoQ10

Patients will begin taking their study pills (CoQ10 placebo) on the morning of Cycle 2 Day 3 (11-15 days prior to Cycle 3), and will continue taking the study pills through the morning of their Cycle 3 infusion (Day 1 Cycle 3). Patients will then be crossed-over to the alternative condition. On the morning of Cycle 3 Day 3, patients will begin taking their study pills (CoQ10) and will continue taking the study pills through the morning of their Cycle 4 infusion (Day 1 Cycle 4).

Infusion will be standard of care chemotherapy with doxorubicin and cyclophosphamide.

Group Type: EXPERIMENTAL

CoQ10

Intervention Type: DRUG

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d CoQ10 (2 capsules) Dose Level 2: 600mg/d CoQ10 (4 capsules) Dose Level 3: 1200mg/d CoQ10 (8 capsules)

CoQ10 Placebo

Intervention Type: OTHER

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d placebo (2 capsules) Dose Level 2: 600mg/d placebo (4 capsules) Dose Level 3: 1200mg/d placebo (8 capsules)

Doxorubicin

Intervention Type: DRUG

Standard of care chemotherapy medication used to treat cancer.

Cyclophosphamide

Intervention Type: DRUG

Standard of care chemotherapy medication used to treat cancer.

Interventions

CoQ10

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d CoQ10 (2 capsules) Dose Level 2: 600mg/d CoQ10 (4 capsules) Dose Level 3: 1200mg/d CoQ10 (8 capsules)

Intervention Type: DRUG

CoQ10 Placebo

Capsules taken daily for two weeks prior to Cycle 3 chemotherapy infusion OR Capsules taken daily for two weeks prior to Cycle 4 infusion.

Dose Level 1: 300mg/d placebo (2 capsules) Dose Level 2: 600mg/d placebo (4 capsules) Dose Level 3: 1200mg/d placebo (8 capsules)

Intervention Type: OTHER

Doxorubicin

Standard of care chemotherapy medication used to treat cancer.

Intervention Type: DRUG

Cyclophosphamide

Standard of care chemotherapy medication used to treat cancer.

Intervention Type: DRUG

Other Intervention Names

Coenzyme Q10; Coenzyme Q10 Placebo; Doxil; Cytoxan

Eligibility Criteria

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).

• Minimum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heather Greenlee, ND, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAD8521

Identifier Type: -

Identifier Source: org_study_id