Capecitabine With Digoxin for Metastatic Breast Cancer

• Sponsor: Western Regional Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01887288
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

To evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Capecitabine; Drug: Digoxin	Phase 2

Detailed Description

In this phase II study, the Investigators will combine metronomic capecitabine with digoxin to treat metastatic breast cancer patients who have progressed on both anthracyclines and taxanes. We hypothesize that the combination of digoxin with metronomic capecitabine may lead to increased efficacy and duration of treatment without progression with decreased side effects than standard regimen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metronomic Capecitabine With Digoxin for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Capecitabine with Digoxin Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks)	Drug: Capecitabine; 650 mg/m^2 PO b.i.d.; Other Names: Xeloda® ; Drug: Digoxin; 0.25 mg once daily; Other Names: Cardoxin® Digitek® Lanoxicaps® Lanoxin®

Outcome Measures

Primary Outcome Measures

1. Metronomic Capecitabine With Oral Digoxin [One year]

   Evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer

Secondary Outcome Measures

1. Combination Overall Clinical Benefit by RECIST 1.1 [One year]

   Assess the activity of this combination in terms of overall clinical benefit rates (CBR), including complete response (CR), partial response (PR) or stable disease (SD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients ≥ 18 years of age with histologically confirmed, metastatic breast cancer resistant to anthracyclines and taxanes

2. Anthracycline resistance is defined as tumor progression during treatment or within 3 months of last dose in the metastatic setting, or recurrence within 6 months in the neoadjuvant or adjuvant setting. Alternatively, a minimum cumulative dose of anthracycline of 240 mg/m^{2 (doxorubicin) or 360 mg/m}2 (epirubicin) has been reached, or there is contraindication to use anthracycline, the patient is also eligible

3. Taxane resistance is defined as recurrence within 4 months of the last dose in the metastatic setting or within 12 months in the adjuvant setting

4. Having progressed on anti-HER2 or hormonal therapy if they have HER2 positive or hormone-receptor positive breast cancer

5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2 and a life expectancy >3 months.

6. Participants must have at least one target lesion as defined by RECIST 1.1 that allows for evaluation of tumor response

7. Absolute neutrophil count ≥ 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL

8. Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of normal range

9. No remaining grade 2 or higher toxicity from prior cancer therapies unless judged to be clinically insignificant by the Principal Investigator

10. At least three (3) weeks from prior chemotherapy

11. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.

Exclusion Criteria:

1. Inadequate renal function with a calculated creatinine clearance less than 51 mL/min.

2. History of ventricular fibrillation, sinus node or AV nodal disease, Wolff Parkinson White Syndrome, hemodynamically significant or life threatening cardiac arrhythmia.

3. Uncontrolled cardiac disease, congestive heart failure, angina or hypertension.

4. Myocardial infarction or unstable angina within 2 months of treatment.

5. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C (patients are NOT required to be tested for the presence of such viruses prior to therapy on this protocol).

6. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

7. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

8. Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.

9. Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.

10. Serious non-healing wound, ulcer, or bone fracture.

11. Major surgery or significant traumatic injury within 2 weeks of first study drug.

12. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements.

13. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements.

14. Currently on anti-coagulation therapy with Coumadin, and cannot be switched other forms of anti-coagulation.

15. Patients have symptomatic untreated brain metastasis or leptomeningeal metastases or treated but still symptomatic requiring the use of steroid within the past two weeks.

16. Patients receiving any other investigational agents. Pregnant or Lactating females.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Regional Medical Center	Goodyear	Arizona	United States	85338

Sponsors and Collaborators

• Western Regional Medical Center

Investigators

• Principal Investigator: Jiaxin Niu, MD, PhD, Western Regional Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Western Regional Medical Center
• ClinicalTrials.gov Identifier: NCT01887288
• Other Study ID Numbers: WRMC 13-05
• First Posted: Jun 26, 2013
• Last Update Posted: Feb 22, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine; Digoxin

Study Results

Participant Flow

Arm/Group Title	Capecitabine With Digoxin
Arm/Group Description	Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks) Capecitabine: 650 mg/m^2 PO b.i.d. Digoxin: 0.25 mg once daily
Period Title: Overall Study
STARTED	16
COMPLETED	0
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Capecitabine With Digoxin
Arm/Group Description	Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks) Capecitabine: 650 mg/m^2 PO b.i.d. Digoxin: 0.25 mg once daily
Overall Participants	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Metronomic Capecitabine With Oral Digoxin
Description	Evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer
Time Frame	One year

Outcome Measure Data

Analysis Population Description

data were not collected

Arm/Group Title	Capecitabine With Digoxin
Arm/Group Description	Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks) Capecitabine: 650 mg/m^2 PO b.i.d. Digoxin: 0.25 mg once daily
Measure Participants	0

2. Secondary Outcome

Title	Combination Overall Clinical Benefit by RECIST 1.1
Description	Assess the activity of this combination in terms of overall clinical benefit rates (CBR), including complete response (CR), partial response (PR) or stable disease (SD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame	One year

Outcome Measure Data

Analysis Population Description

data were not collected

Arm/Group Title	Capecitabine With Digoxin
Arm/Group Description	Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks) Capecitabine: 650 mg/m^2 PO b.i.d. Digoxin: 0.25 mg once daily
Measure Participants	0

Adverse Events

Time Frame	data were not collected
Adverse Event Reporting Description	data were not collected
Arm/Group Title	Capecitabine With Digoxin
Arm/Group Description	Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle (1 cycle - 4 weeks) Capecitabine: 650 mg/m^2 PO b.i.d. Digoxin: 0.25 mg once daily
All Cause Mortality
	Capecitabine With Digoxin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Capecitabine With Digoxin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Capecitabine With Digoxin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.