Study of Pyridoxine for Hand-Foot Syndrome

• Sponsor: Asan Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00446147
• Collaborator: (none)
• Enrollment: 389
• Arms: 2
• Duration (Months): 30

Study Details

Study Description

Brief Summary

Although pyridoxine has been used empirically for the prevention of capecitabine associated hand-foot syndrome (HFS), its efficacy needs to be demonstrated in prospective controlled trials. The investigators therefore performed a prospective randomized double-blind study to determine whether pyridoxine 200 mg/day can prevent the development of HFS when given concurrently with capecitabine. The investigators also tested the ability of pyridoxine to treat primary occurrence of grade 2-3 HFS.

Condition or Disease	Intervention/Treatment	Phase
Hand-foot Syndrome	Drug: Pyridoxine; Drug: Placebo	Phase 3

Detailed Description

Although pyridoxine has been used empirically for the prevention of capecitabine associated HFS, its efficacy needs to be demonstrated in prospective controlled trials. We estimated that the HFS rate with placebo and pyridoxine would be 0.35 and 0.18, respectively, and we therefore calculated that a sample size of 345 patients would be necessary to detect these hazard rates with an 80% power (β=0.2) and two-sided significance level of α=0.05. We assumed a follow up loss rate of 10%, thus requiring 380 patients to be randomized. Chemotherapy-naive patients with gastrointestinal tract cancers who were scheduled for capecitabine-containing chemotherapy were assigned to receive oral pyridoxine or placebo in randomized double-blind placebo controlled study. Pyridoxine 100 mg b.i.d was prescribed to the patients in the pyridoxine group, identical placebo 100 mg b.i.d was prescribed in the placebo group by the closed envelop randomization. Patients were stratified by chemotherapy regimen: capecitabine alone (X), capecitabine and cisplatin (XP), or docetaxel, capecitabine, and cisplatin (DXP). Patients were observed until NCI CTC grade 2 or 3 HFS developed or capecitabine-containing chemotherapy ended. Patients in the placebo group who developed grade 2 or 3 HFS were randomized to receive pyridoxine or placebo for the next chemotherapy cycle to determine whether pyridoxine could improve HFS, and the same treatment was continued for 2 chemotherapy cycles.

Study Design

• Study Type: Interventional
• Actual Enrollment: 389 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Double-Blind Phase III Study of Pyridoxine vs Placebo for the Prevention of Capecitabine-induced Hand-Foot Syndrome
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Dec 1, 2006
• Actual Study Completion Date: Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo one tablet twice per day, which is identical to pyridoxine	Drug: Placebo; placebo 100mg BID/daily, Per oral
Experimental: Pyridoxine 100 mg twice per day	Drug: Pyridoxine; 100mg BID/daily, Per oral

Outcome Measures

Primary Outcome Measures

1. Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome [Up to 2 years]

   A total administered dose of capecitabine until the development of grade 2 or higher hand-foot syndrome during the chemotherapy.

Secondary Outcome Measures

1. Number of Patients With Hand-foot Syndrome [Up to 2 years]

   Number of patients with any grade of hand-foot syndrome

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Gastrointestinal tract cancer patients treated with capecitabine-containing chemotherapy as a first-line treatment were randomly allocated to concurrent treatment with pyridoxine or placebo.

• All patients were 18 to 70 years old

• Had Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower

• An estimated life expectancy > 3 months

• Adequate bone marrow function, including white blood cell (WBC) count of >3500 cells/㎕ and platelet count of >100000/㎕

• Adequate renal function (serum creatinine concentration <1.5 mg/㎗)

• Adequate liver function with (serum bilirubin concentration <1.5 mg/㎗, transaminase <3 times the upper normal limit, and serum albumin >2.5 mg/㎗).

Exclusion Criteria:

• Previous treatment for HFS

• Hypersensitivity to pyridoxine

• A combination of other malignancies

• Serious illnesses or medical conditions

• Immune suppression or positive human immunodeficiency virus (HIV) serology

• Pregnant or lactating women.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Asan Medical Center

Investigators

• Principal Investigator: Yoon-Koo Kang, Asan Medical Center IRB

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yoon-Koo Kang, Oncologist, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT00446147
• Other Study ID Numbers: AMC-ONCGI-0403
• First Posted: Mar 12, 2007
• Last Update Posted: Feb 25, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Yoon-Koo Kang, Oncologist, Asan Medical Center: hand-foot syndrome; capecitabine; pyridoxine; prevention
• Additional relevant MeSH terms: Hand-Foot Syndrome; Syndrome; Pyridoxine

Study Results

Participant Flow

Arm/Group Title	Placebo	Pyridoxine
Arm/Group Description	one tablet twice per day, which is identical to pyridoxine Placebo: placebo 100mg BID/daily, Per oral	100 mg twice per day Pyridoxine: 100mg BID/daily, Per oral
Period Title: Overall Study
STARTED	195	194
COMPLETED	180	180
NOT COMPLETED	15	14

Baseline Characteristics

Arm/Group Title	Placebo	Pyridoxine	Total
Arm/Group Description	one tablet twice per day, which is identical to pyridoxine Placebo: placebo 100mg BID/daily, Per oral	100 mg twice per day Pyridoxine: 100mg BID/daily, Per oral	Total of all reporting groups
Overall Participants	180	180	360
Age, Customized (years) [Median (Full Range) ]
Age_median	56	56	56
Sex: Female, Male (Count of Participants)
Female	76 42.2%	59 32.8%	135 37.5%
Male	104 57.8%	121 67.2%	225 62.5%
Region of Enrollment (participants) [Number]
Korea, Republic of	180 100%	180 100%	360 100%

Outcome Measures

1. Primary Outcome

Title	Cumulative Dose of Capecitabine Until the Development of Grade 2 or Higher Hand-foot Syndrome
Description	A total administered dose of capecitabine until the development of grade 2 or higher hand-foot syndrome during the chemotherapy.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Pyridoxine
Arm/Group Description	one tablet twice per day, which is identical to pyridoxine Placebo: placebo 100mg BID/daily, Per oral	100 mg twice per day Pyridoxine: 100mg BID/daily, Per oral
Measure Participants	180	180
Median (95% Confidence Interval) [miligram per square meter]	70000	70000

2. Secondary Outcome

Title	Number of Patients With Hand-foot Syndrome
Description	Number of patients with any grade of hand-foot syndrome
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Pyridoxine
Arm/Group Description	one tablet twice per day, which is identical to pyridoxine Placebo: placebo 100mg BID/daily, Per oral	100 mg twice per day Pyridoxine: 100mg BID/daily, Per oral
Measure Participants	180	180
Number [participants]	55 30.6%	57 31.7%

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Placebo		Pyridoxine
Arm/Group Description	one tablet twice per day, which is identical to pyridoxine Placebo: placebo 100mg BID/daily, Per oral		100 mg twice per day Pyridoxine: 100mg BID/daily, Per oral
All Cause Mortality
	Placebo		Pyridoxine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pyridoxine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/180 (0%)		0/180 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Pyridoxine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/180 (0%)		0/180 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.