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

• Sponsor: Gerald Higa, PharmD. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01499940
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 11
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief 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). 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.

Condition or Disease	Intervention/Treatment	Phase
Neurotoxicity	Drug: Vitamin D3	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Phase II Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through the Vitamin D Pathway
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Vitamin D3 2000 IU/day 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; 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.; Other Names: Cholecalciferol

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Peripheral Neurotoxic Reactions [Up to 12 months]

   NCI CTCAE Version 4.0

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West Virginia University Hospitals Mary Babb Randolph Cancer Center	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• Gerald Higa, PharmD.

Investigators

• Principal Investigator: Gerald Higa, PharmD, West Virginia University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bischoff-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. Review. Erratum in: Am J Clin Nutr. 2006 Nov;84(5):1253. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. Am J Clin Nutr. 2007 Sep;86(3):809. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.
• Heaney 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. Review.
• Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. Review.
• 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.
• Wang 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.

• Responsible Party: Gerald Higa, PharmD., Associate Professor, West Virginia University
• ClinicalTrials.gov Identifier: NCT01499940
• Other Study ID Numbers: WVU 11011
• First Posted: Dec 26, 2011
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Gerald Higa, PharmD., Associate Professor, West Virginia University: peripheral neuropathy; vitamin D status; oxaliplatin
• Additional relevant MeSH terms: Neurotoxicity Syndromes; Vitamin D; Cholecalciferol

Study Results

Participant Flow

Arm/Group Title	Vitamin D3 2000 IU/Day
Arm/Group Description	Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study Vitamin D3: 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.
Period Title: Overall Study
STARTED	9
COMPLETED	0
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Vitamin D3 2000 IU/Day
Arm/Group Description	Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study Vitamin D3: 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.
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 44.4%
>=65 years	5 55.6%
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	9 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Peripheral Neurotoxic Reactions
Description	NCI CTCAE Version 4.0
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D3 2000 IU/Day
Arm/Group Description	Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study Vitamin D3: 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.
Measure Participants	9
Count of Participants [Participants]	5 55.6%

Adverse Events

Arm/Group Title	Vitamin D3 2000 IU/Day
Arm/Group Description	Vitamin D3 2000 IU/day on day of 1st cycle of oxaliplatin; continue as long as patient treated with oxaliplatin and remains on study Vitamin D3: 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.
All Cause Mortality
	Vitamin D3 2000 IU/Day
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Serious Adverse Events
	Vitamin D3 2000 IU/Day
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D3 2000 IU/Day
	Affected / at Risk (%)	# Events
Total	0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.