NeurotoxicityPhase 2NCT01499940
Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through Vitamin D Pathway
A Phase 2 study testing Vitamin D3 in people with Neurotoxicity, run by Gerald Higa, PharmD. at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Neurotoxicity
- What is being tested?
- Vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
West Virginia University Hospitals Mary Babb Randolph Cancer Center
Morgantown, West Virginia, 26506
About this study
Official title: Phase II Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through the Vitamin D Pathway
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.
Read the detailed description
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.
- Conditions
- Neurotoxicity
- Being tested
- Vitamin D3
- Keywords
- peripheral neuropathy, vitamin D status, oxaliplatin
- Medical subject headings
- Neurotoxicity Syndromes, Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3Drug
Also called Cholecalciferol
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.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D3 2000 IU/day | Experimental | Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study Receives: Drug: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Peripheral Neurotoxic Reactions
NCI CTCAE Version 4.0
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: Research cancelled - no funding identified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for NeurotoxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gerald Higa, PharmD.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gerald Higa, PharmD., West Virginia University
- Investigators
- Gerald Higa, PharmD, Principal investigator, West Virginia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499940
- Sponsor's protocol ID
- WVU 11011
- Status last verified
- Nov 2021
- First submitted
- 18 Oct 2011
- Last updated
- 10 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kim JS, Ryu SY, Yun I, Kim WJ, Lee KS, Park JW, Kim YI. 1alpha,25-Dihydroxyvitamin D(3) Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation. J Clin Neurol. 2006 Dec;2(4):252-7. doi: 10.3988/jcn.2006.2.4.252. Epub 2006 Dec 20.
PubMed 20396528Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang Y. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001 Jun 15;904(1):67-75. doi: 10.1016/s0006-8993(01)02450-7.
PubMed 11516412Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. doi: 10.1093/ajcn/84.1.18.
PubMed 16825677Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.
PubMed 17634462Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1706S-9S. doi: 10.1093/ajcn/80.6.1706S.
PubMed 15585791
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through the Vitamin D Pathway
- ClinicalTrials.gov ID
- NCT01499940
- Acronym / sponsor ID
- WVU 11011
- Conditions
- Neurotoxicity
- Keywords
- peripheral neuropathy, vitamin D status, oxaliplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Research cancelled - no funding identified.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Gerald Higa, PharmD.University, hospital or other
- Study start
- Jan 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Posted 5 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 2000 IU/day | Experimental | Drug: Vitamin D3Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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,
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3Also: CholecalciferolVitamin 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. | Drug | Vitamin D3 2000 IU/day |
Primary outcome
Number of Participants With Peripheral Neurotoxic Reactions
Time frame: Up to 12 months
NCI CTCAE Version 4.0
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20396528Kim JS, Ryu SY, Yun I, Kim WJ, Lee KS, Park JW, Kim YI. 1alpha,25-Dihydroxyvitamin D(3) Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation. J Clin Neurol. 2006 Dec;2(4):252-7. doi: 10.3988/jcn.2006.2.4.252. Epub 2006 Dec 20.
- Background: PubMed 11516412Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang Y. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001 Jun 15;904(1):67-75. doi: 10.1016/s0006-8993(01)02450-7.
- Background: PubMed 16825677Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. doi: 10.1093/ajcn/84.1.18.
- Background: PubMed 17634462Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.
- Background: PubMed 15585791Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1706S-9S. doi: 10.1093/ajcn/80.6.1706S.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald Higa, PharmD principal investigator
West Virginia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin D3 in people with Neurotoxicity, run by Gerald Higa, PharmD. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Peripheral Neurotoxic Reactions (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01499940, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2021.