Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through Vitamin D Pathway

Study Overview
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Brief Summary
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Many patients with cancer that are treated with a drug called oxaliplatin. This drug is used with other drugs to treat cancer. The drug can cause problems with the nerves in the hands and feet called peripheral neuropathy (a side effect of the drug). Peripheral neuropathy may make the hands and feet feel like they are tingling, have a burning feeling, and can cause pain. Almost all patients who receive oxaliplatin as part of their cancer treatment have peripheral neuropathy. Patients who do have this side effect usually have to take a lower dose of or stop taking the oxaliplatin even if the drug is helping their cancer. So far there is not a lot of information about how to make this side effect better or help it go away completely. There is some information that low levels of Vitamin D in the blood might be linked to problems or diseases of the nervous system like multiple sclerosis or Parkinson's Disease. It is even thought that Vitamin D may help protect the cells in the nervous system. Because of this information, researchers want to see if giving patients Vitamin D while they are receiving the drug oxaliplatin to see if it helps prevent the side effect peripheral neuropathy. Patients taking oxaliplatin who want to be in this study will take one Vitamin D capsule each day while they take oxaliplatin. Being in this study will not affect how the patient's cancer is treated. There are blood tests in the study to check Vitamin D levels and for a protein called nerve growth factor (NGF). The study team will carefully monitor the patients for any signs of oxaliplatin-related neurologic toxicity during the study.

Detailed Description
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Oxaliplatin is used most frequently in patients with metastatic and early-stage colorectal cancers. It has been found that in the adjuvant setting, Oxaliplatin improves both disease free and overall survival. Despite these results, the use of Oxaliplatin is limited by the sensory neuropathy or numbness and tingling, that occurs in 80% -90% of patients. Some of these patients will develop irreversible and debilitating neuropathy, in which the drug may no longer be used to treat their cancer. It is expected that this proposed study will provide new information for the role of Vitamin D in the pathogenesis of Oxaliplatin-induced neurotoxicity. The dynamic effects of Vitamin D on calcium and nerve growth factor plus the now recognized state of subclinical Vitamin D deficiency are compelling pieces of evidence that indicate this hormone may be in a pivotal position in the multifactorial pathogenesis of neurotoxic reactions induced by Oxaliplatin. The specific aim of the study is to determine the neuroprotective effects of Vitamin D. Patients will receive Oxaliplatin at a dose of 80 mg/m2 at a physician determined frequency appropriate for the underlying malignancy, which can be any histological diagnosis of a malignant solid neoplasm involving the GI tract not restricted to the colon, rectum and esophagus. Blood will be collected to monitor the level of Vitamin D and nerve growth factor (NGF) at specific time points. Vitamin D levels will be checked once a month and NGF levels will be checked bi-weekly. These blood samples will be collected at the same time of the patients routine blood draws. Patients will take one capsule containing 2000 IUs of Vitamin D3 daily, beginning up to 7 days prior to the first dose of Oxaliplatin. Vitamin D3 will be provided to patients as long as they remain on the study.

Official Title
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Phase II Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through the Vitamin D Pathway

Conditions
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Neurotoxicity

Intervention / Treatment
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* Drug: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a histologic diagnosis of a malignant solid neoplasm involving the gastrointestinal tract not necessarily restricted to the colon, rectum, and esophagus, Will receive oxaliplatin-based chemotherapy for the first time (previous treatment with non-oxaliplatin-based chemotherapy does not preclude eligibility), Have disease of any stage and will be treated according to established standards, Have a performance status (ECOG) of 2 or less, Have intact organ function as determined by laboratory tests of the kidney, liver, and bone marrow deemed appropriate to receive cytotoxic chemotherapy, Are 18 years of age or older, and Have signed a consent and information form to participate in the study. Exclusion Criteria: Are pregnant (subjects of childbearing age will have a pregnancy test performed), Are taking calcitriol or have vitamin D levels that are >100 ng/dL, Are receiving medication for seizures, or Have pre-existing peripheral neuropathy grade >1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 2000 IU/day<br>Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study | Drug: Vitamin D3<br>* Vitamin D3 will be administered at a dose of 2000 IU orally daily starting on day 1 of the first cycle of oxaliplatin. The vitamin will be continued at this dose and schedule for approximately 6 months if the patient is receiving oxaliplatin in the adjuvant setting and neither dosage nor interval has been modified for neurological toxicity. The duration of therapy if oxaliplatin is given for metastatic disease will vary. Nonetheless, the study vitamin will be continued using the same criteria as in the adjuvant setting.<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peripheral Neurotoxic Reactions | NCI CTCAE Version 4.0 | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral neuropathy, vitamin D status, oxaliplatin