A Randomized Phase III Study of Vitamins B6 and B12 to Prevent Chemotherapy-Induced Neuropathy in Cancer Patients

Study Overview
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Brief Summary
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Many types of chemotherapy may cause nerve damage as a side effect. This neurotoxicity can manifest as peripheral sensory neuropathy (characterized by numbness, tingling, or pain). The goal of this study is to determine the efficacy of the combination of vitamin B6 and B12 in preventing chemotherapy induced neuropathy.

Detailed Description
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Neuropathy can be a significant side effect of chemotherapy using platinum compounds, taxanes, and vinca alkaloids. There is clinical and preclinical data that vitamin B6 and B12 may alleviate neuropathy in experimentally induced neuropathy in animal models, or clinical neuropathy such as diabetic neuropathy. This is a randomized phase III study of the use of multivitamins with or without vitamin B6 and B12 to prevent or relieve neuropathic toxicity from chemotherapy in patients receiving chemotherapy. Patients will be stratified by type of chemotherapy agent (3 groups), presence or absence of neuropathy at baseline, and randomized to receive placebo or vitamin B6/B12 supplementation.

Official Title
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A Randomized Phase III Study of Vitamins B6 and B12 to Prevent Chemotherapy-Induced Neuropathy in Cancer Patients.

Conditions
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Cancer

Intervention / Treatment
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* Dietary Supplement: Multivitamin (MV)
* Dietary Supplement: Multivitamin + Vitamin B12 + Vitamin B6
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients, 18 years of age or older, with a cancer treated with any of the following drugs are eligible: Taxanes, vinca alkaloid analogs, heavy metals. Each patient will be allocated to the following 3 groups: Group 1 (Heavy metals): Patients treated with cisplatin (>25 mg/m2/week dose intensity) or oxaliplatin Group 2 (Taxane): Patients treated with paclitaxel, docetaxel or abraxane Group 3 (Vinca alkaloids): Patients treated with vincristine and vinorelbine. Patients must have a life expectancy of at least 24 weeks. Patients must have a Zubrod performance status of 0-2. Patients must sign an informed consent. Patients may have a grade 0 (chemotherapy naive) or 1 neuropathy (history of prior chemotherapy) prior to entry. Exclusion Criteria: Patients with symptomatic brain metastases are excluded from this study. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. Patients may receive no other concurrent complementary medicines during this study. Patients with neuropathy induced diabetes are not eligible for this study Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Multivitamin (MV)<br>1 multivitamin pill will be taken orally, daily starting on the first day of chemotherapy and continuing for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts) | Dietary Supplement: Multivitamin (MV)<br>* Multivitamins containing no more than 10 mg of pyridoxine and/or 10 micrograms of Vitamin B12 will be given to the patients on this arm.<br>Drug: Chemotherapy<br>* Patients are treated per standard of care according to the choice of the treating physician with heavy metals (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), or vinca alkaloids (vincristine, vinorelbine) Ranges of cumulative doses (in mg/m2) are: paclitaxel, 700-960; docetaxel, 240-400; vincristine, 8-16; vinorelbine, 360-480; cisplatin, 240-400; oxaliplatin, 400-800; abraxane, 1200-1800<br>* Other names: Vinorelbine tartrate (Navelbine);|
| Experimental: Multivitamin + Vitamin B12 + Vitamin B6<br>1 multivitamin pill will be taken orally, daily starting on the first day of chemotherapy and continuing for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts). The patient will also take the following, starting on the first day of chemotherapy: pyridoxine 50 mg three times per day, orally and continue for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts) Vitamin B12 one mg injected intramuscularly, every 3 or 4 weeks, depending on the timing of the chemotherapy for 4 doses. | Dietary Supplement: Multivitamin + Vitamin B12 + Vitamin B6<br>* Multivitamin (containing no more than 10 mg of pyridoxine and/or 10 micrograms of Vitamin B12), plus Vitamin B6 tablets and Vitamin B12 injections<br>Drug: Chemotherapy<br>* Patients are treated per standard of care according to the choice of the treating physician with heavy metals (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), or vinca alkaloids (vincristine, vinorelbine) Ranges of cumulative doses (in mg/m2) are: paclitaxel, 700-960; docetaxel, 240-400; vincristine, 8-16; vinorelbine, 360-480; cisplatin, 240-400; oxaliplatin, 400-800; abraxane, 1200-1800<br>* Other names: Vinorelbine tartrate (Navelbine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurotoxicity Assessment at Baseline | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline (prior to chemotherapy treatment) and the mean total score for all patients is reported. | At study start; prior to treatment (week 0) | 
| Neurotoxicity Assessment at Cycle 2 | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to complete at completion of cycle 2 of chemotherapy treatment and the mean total score for all patients is reported. | 2 weeks | 
| Neurotoxicity Assessment at Cycle 4 | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 16 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at completion of cycle 4 of their chemotherapy treatment and the mean total score for all patients is reported. | 4 weeks | 
| Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline, cycle 2, and cycle 4 of their chemotherapy treatment. Change in neurotoxicity scores from baseline to the completion of 4 cycles are reported as the mean total score for all patients. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin B-12, Vitamin B-6, Chemotherapy-Induced Neuropathy, Taxanes, Vinca alkaloid, Heavy metals, Neuropathy, Nerve pain