Trial Outcomes & Findings for Capecitabine in Treating Patients With Metastatic Breast Cancer (NCT NCT00274768)

Last Updated: 2020-01-27

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Participants were followed to progression, evaluated every 12 weeks

Results posted on

2020-01-27

Participant Flow

Thirty patients with metastatic breast cancer were consented between August 2005 and December 2008. Twenty six patients were eligible and initiated treatment on-study.

Women (≥ 18 or older) with a histologically confirmed metastatic (stage 4) adenocarcinoma of the breast were eligible. Several inclusion and exclusion applied to confirm that women were appropriate to take part in the study intervention.

Participant milestones

Participant milestones
Measure	Capecitabine The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Overall Study STARTED	26
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Capecitabine in Treating Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Capecitabine n=26 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were followed to progression, evaluated every 12 weeks

Population: Any participant who completed at least one (1) cycle of capecitabine administration was evaluable for response.

Outcome measures

Outcome measures
Measure	Capecitabine n=21 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Response Rate	21 participants

SECONDARY outcome

Timeframe: 3-week cycles of treatment up to 16 cycles

Population: Five patients did not complete cycle 1

The overall clinical benefit rate as assessed by number of participants with lack of progression for at least 24 weeks.

Outcome measures

Outcome measures
Measure	Capecitabine n=21 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks	4 Participants

SECONDARY outcome

Timeframe: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours

Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-fluorouracil (FU)\] assessed using maximum plasma concentration (Cmax) in ng/mL.

Outcome measures

Outcome measures
Measure	Capecitabine n=26 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration Capecitabine	9324 ng/mL Standard Deviation 7015
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration 5'-DFCR	6353 ng/mL Standard Deviation 2590
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration 5'-DFUR	4597 ng/mL Standard Deviation 2608
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration 5-FU	753 ng/mL Standard Deviation 1209

SECONDARY outcome

Timeframe: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours

Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-FU\] assessed using AUC in ng\*h/mL.

Outcome measures

Outcome measures
Measure	Capecitabine n=26 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) Capecitabine	7255 ng*h/mL Standard Deviation 4180
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) 5'-DFCR	11344 ng*h/mL Standard Deviation 5583
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) 5'-DFUR	6653 ng*h/mL Standard Deviation 2166
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) 5-FU	1230 ng*h/mL Standard Deviation 1826

SECONDARY outcome

Timeframe: 3-week cycles of treatment up to 16 cycles

This was assessed by number of participants who did not miss any doses of Capecitabine during treatment using the Medication Event Monitoring System (MEMS).

Outcome measures

Outcome measures
Measure	Capecitabine n=26 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Adherence and Compliance to Oral Medication Using Electronic Monitoring	13 Participants

SECONDARY outcome

Timeframe: 3-week cycles of treatment up to 16 cycles

Population: Five patients did not complete cycle 1

Time to treatment failure in weeks

Outcome measures

Outcome measures
Measure	Capecitabine n=21 Participants The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Time to Treatment Failure	12 weeks Interval 6.0 to 48.0

Adverse Events

Capecitabine

Serious events: 2 serious events

Other events: 20 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Capecitabine n=26 participants at risk The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death	7.7% 2/26 • Number of events 2 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.

Other adverse events

Other adverse events
Measure	Capecitabine n=26 participants at risk The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent.
Blood and lymphatic system disorders Hemoglobin	11.5% 3/26 • Number of events 3 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
General disorders Fatigue	61.5% 16/26 • Number of events 16 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Metabolism and nutrition disorders Anorexia	19.2% 5/26 • Number of events 5 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Nausea	53.8% 14/26 • Number of events 14 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
General disorders Vomiting	23.1% 6/26 • Number of events 6 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Diarrhea	26.9% 7/26 • Number of events 7 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Constipation	7.7% 2/26 • Number of events 2 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Dyspepsia	23.1% 6/26 • Number of events 6 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Nervous system disorders Dysgeusia	7.7% 2/26 • Number of events 2 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Mucositis oral	23.1% 6/26 • Number of events 6 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Gastrointestinal disorders Abdominal pain	15.4% 4/26 • Number of events 4 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	76.9% 20/26 • Number of events 20 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.7% 2/26 • Number of events 2 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Nervous system disorders Headache	19.2% 5/26 • Number of events 5 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.
Nervous system disorders Peripheral sensory neuropathy	11.5% 3/26 • Number of events 3 • Participants were evaluated for adverse events every cycle, or every 3 weeks; median length of time on trial was 7 cycles (or 21 weeks). Potentially treatment-related toxicities of all grades and for all cycles are listed.

Additional Information

Dr. Antonio Wolff

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 410-614-6192

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place