Venlafaxine in Preventing Chronic Oxaliplatin-Induced Neuropathy In Patients Receiving Combination Chemotherapy

September 4, 2019 updated by: Mayo Clinic

A Pilot Randomized, Placebo-controlled, Double Blind Study of Venlafaxine to Prevent Oxaliplatin-Induced Neuropathy

You are being asked to take part in this research study because you are going to be treated with oxaliplatin chemotherapy as part of your standard care. Oxaliplatin commonly causes neuropathy (numbing, tingling and/or pain).The purpose of this study is to compare the effects, good and/or bad, of venlafaxine with a placebo (an inactive agent) on oxaliplatin-induced neuropathy (numbing, tingling and/or pain)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To explore whether venlafaxine can prevent or ameliorate chronic, cumulative neurotoxicity associated with oxaliplatin in cancer patients receiving oxaliplatin, fluorouracil, leucovorin calcium (FOLFOX).

SECONDARY OBJECTIVES:

I. To explore whether venlafaxine can ameliorate acute neuropathy associated with oxaliplatin.

TERTIARY OBJECTIVES:

I. To explore whether venlafaxine can increase the cumulative oxaliplatin doses that can be delivered without dose-limiting chronic neurotoxicity.

II. To explore whether venlafaxine causes adverse events in this setting. III. To explore whether the neuropathy data provided by the Rydel-Seiffer graduated tuning fork is consistent with patient-reported outcome (PRO) measures of chemotherapy-induced peripheral neuropathy (CIPN) and whether this tool might cause different results in patients receiving venlafaxine versus placebo.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive venlafaxine orally (PO) twice daily (BID) beginning on day 1 of and continuing through completion of FOLFOX.

ARM II: Patients receive placebo PO BID beginning on day 1 of and continuing through completion of FOLFOX.

After completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Scheduled to receive FOLFOX chemotherapy with individual oxaliplatin doses of 85 mg/m^2 per cycle given in 2 week cycles (e.g. modified [m] FOLFOX6 or FOLFOX4) Adequate complete blood count (CBC) and creatinine values (per attending physician) obtained =< 28 days prior to registration Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential Ability to complete questionnaire(s) by themselves or with assistance Life expectancy >= 4 months Strong inhibitors of CYP3A4: > 5-fold increase in the plasma area under the curve (AUC) values or more than 80 % decrease in clearance

    • Indinavir (Crixivan®)
    • Nelfinavir (Viracept®)
    • Atazanavir (Reyataz®)
    • Ritonavir (Norvir®)
    • Clarithromycin (Biaxin®, Biaxin XL®)
    • Itraconazole (Sporanox®)
    • Ketoconazole (Nizoral®)
    • Nefazodone (Serzone®)
    • Saquinavir (Fortovase®, Invirase®)
    • Telithromycin (Ketek®) Inducers of CYP3A4
    • Efavirenz (Sustiva®)
    • Nevirapine (Viramune®)
    • Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
    • Modafinil (Provigil®)
    • Phenobarbital (Luminal®)
    • Phenytoin (Dilantin®, Phenytek®)
    • Pioglitazone (Actos®)
    • Rifabutin (Mycobutin®)
    • Rifampin (Rifadin®)
    • St. John's wort

Exclusion Criteria:

Any of the following:

  • Pregnant women
  • Nursing women History of an allergic reaction to, or intolerance of, venlafaxine Treatment =< 7 days with other antidepressants, anticonvulsants, monoamine oxidase (MAO) inhibitors, or other neuropathic pain medication agents such as carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine; in addition, they may not be taking other agents for the treatment of neuropathy, nor other known moderate or strong CYP 2D6 (which consist of Cinacalcet [Sensipar™], quinidine, and Terbinafine [Lamisil®, Lamisil AT®]), nor the strong inducer of CYP 2D6 terbinafine (Lamisil®, Lamisil AT®), nor the following drugs that substantially effect CYP 3A4 Moderate inhibitors of CYP3A4: > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance
  • Aprepitant (Emend®)
  • Erythromycin (Erythrocin®, E.E.S. ®, Ery-Tab®, Eryc®, EryPed®, PCE®
  • Fluconazole (Diflucan®)
  • Grapefruit juice
  • Verapamil (Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®)
  • Diltiazem (Cardizem®, Cardizem CD®, Cardizem LA®, Cardizem SR®, Cartia XT™, Dilacor XR®, Diltia XT®, Taztia XT™, Tiazac®) Other medical conditions which, in the opinion of the treating physician/allied health professional, would make this protocol unreasonably hazardous for the patient Prior neurotoxic chemotherapy Concurrent radiotherapy Current (within the last month) pre-existing peripheral neuropathy of any grade Uncontrolled hypertension (defined as 3 consecutive readings over the past year of over 160 systolic, and over 100 diastolic)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I (management of therapy complications)
Patients receive venlafaxine PO BID beginning on day 1 of and continuing through completion of FOLFOX.
Other: questionnaire administration
Ancillary studies
Other: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
Drug: venlafaxine
Given PO
Other Names:
  • Effexor
  • VNF
PLACEBO_COMPARATOR: Arm II (placebo)
Patients receive placebo PO BID beginning on day 1 of and continuing through completion of FOLFOX.
Other: questionnaire administration
Ancillary studies
Other: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
Drug: placebo
Given PO
Other Names:
  • PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cycle 1 Sensory Neuropathy Score (Items 31-36, 39, 40 and 48) of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20
Time Frame: Up to 2 weeks
The EORTC QLQ-CIPN20 sensory neuropathy score will be calculated using the standard algorithm of EORTC QLQ-CIPN20 and transformed into a 0-100 point scale, where high scores meant less symptom burden. The changes of sensory neuropathy from baseline will be derived by subtracting the baseline score from the sensory neuropathy scores at each cycle of evaluation.
Up to 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cycle 1 Acute Neuropathy as Measured by EORTC QLQ CIPN20 Motor Subscale (Items 37, 38, 41-45 and 49), and Autonomic Scale (Items 46, 47, 50)
Time Frame: Up to 2 weeks
The EORTC QLQ-CIPN20 motor and autonomic neuropathy scores will be calculated using the standard algorithm of EORTC QLQ-CIPN20 and transformed into a 0-100 point scale, where high scores meant less symptom burden. The changes of sensory neuropathy from baseline will be derived by subtracting the baseline score from the sensory neuropathy scores at each cycle of evaluation.
Up to 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 17, 2012

Primary Completion (ACTUAL)

March 7, 2014

Study Completion (ACTUAL)

September 23, 2015

Study Registration Dates

First Submitted

May 31, 2012

First Submitted That Met QC Criteria

June 1, 2012

First Posted (ESTIMATE)

June 4, 2012

Study Record Updates

Last Update Posted (ACTUAL)

September 26, 2019

Last Update Submitted That Met QC Criteria

September 4, 2019

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC11C4
  • NCI-2012-00318 (REGISTRY: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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