Clinical trial NCT00486213: Pyridoxine in Preventing Hand-Foot Syndrome Caused by Capecitabine in Patients With Cancer
Official title: Randomized Double-Blind Placebo-Controlled Trial of Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome (HFS)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Dermatologic Complications
Palmar-plantar Erythrodysesthesia
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: dermatologic complications
chemotherapeutic agent toxicity
palmar-plantar erythrodysesthesia
unspecified adult solid tumor, protocol specific
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
First posted: 2007-06-14
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: RATIONALE: Pyridoxine may help prevent hand-foot syndrome caused by capecitabine in patients with cancer. It is not yet known whether pyridoxine is more effective than a placebo in preventing hand-foot syndrome in patients with cancer.

PURPOSE: This randomized phase III trial is studying pyridoxine to see how well it works compared with a placebo in preventing hand-foot syndrome caused by capecitabine in patients with cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the incidence of capecitabine-induced palmar-plantar erythrodysesthesia (hand-foot syndrome \[HFS\]) ≥ grade 2 in patients with cancer treated with pyridoxine hydrochloride vs placebo.

Secondary

* Compare the time to onset of HFS ≥ grade 2 in patients treated with these regimens.
* Compare the quality of life changes in patients treated with these regimens.
* Identify factors predicting toxicity from capecitabine chemotherapy.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to gender and treatment setting (adjuvant/neoadjuvant vs palliative setting). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Beginning concurrently with planned capecitabine treatment, patients receive oral pyridoxine hydrochloride once daily on days 1-21.
* Arm II: Beginning concurrently with planned capecitabine treatment, patients receive oral placebo once daily on days 1-21.

In both arms, treatment repeats every 21 days for up to 8 courses (until discontinuation of capecitabine treatment).

Quality of life is assessed at baseline, at the beginning of courses 2, 4, 6, and 8, and at the end of the study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of cancer
* Must be receiving single-agent capecitabine either in the adjuvant/neoadjuvant or palliative setting at a dose of ≥ 1000 mg/m² twice daily on days 1-14 (given in 3-week courses)

PATIENT CHARACTERISTICS:

* Life expectancy \> 12 weeks
* No preexisting neuropathy
* No known allergy to pyridoxine hydrochloride and its incipients
* No other dermatologic condition that, in the opinion of the physician, may affect the hands or feet or may complicate evaluation during study treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior capecitabine
* Concurrent radiotherapy, steroids, and/or biological therapy (e.g., trastuzumab \[Herceptin®\] or bevacizumab) allowed provided they do not cause hand-foot syndrome (HFS)
* No other concurrent drugs (e.g., docetaxel or doxorubicin hydrochloride liposome) that can cause HFS
* No concurrent drugs (e.g., oxaliplatin or taxanes) that can cause neuropathy
* No concurrent pyridoxine hydrochloride-containing preparations (e.g., multivitamins or vitamin B complex)
* No concurrent over-the-counter products that contain urea or lactic acid
* No concurrent drugs reported to have drug interactions with pyridoxine hydrochloride (e.g., cycloserine; hydralazine; immunosuppressants; isoniazid; levodopa; estrogen or estrogen-containing contraceptives; penicillamine; phenobarbitone; phenytoin; or pyrazinamide)

Primary outcomes:
measure: First incidence of hand-foot syndrome (HFS) ≥ grade 2 according to NCI CTCAE vs 3.0
timeFrame: up to 8 cycles
Secondary outcomes:
measure: Time to the onset of HFS ≥ grade 2
timeFrame: days to weeks
measure: Quality of life as measured by EuroQOL (EQ-5D) questionnaire
timeFrame: QOL assessment at baseline, at beginning of cycles 2, 4, 6, 8 and at the end of the study.
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
Study officials:
affiliation: National Cancer Centre, Singapore
name: Yoon-Sim Yap, FRACP, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yap YS, Kwok LL, Syn N, Chay WY, Chia JWK, Tham CK, Wong NS, Lo SK, Dent RA, Tan S, Mok ZY, Koh KX, Toh HC, Koo WH, Loh M, Ng RCH, Choo SP, Soong RCT. Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized Clinical Trial. JAMA Oncol. 2017 Nov 1;3(11):1538-1545. doi: 10.1001/jamaoncol.2017.1269.