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

Primary Purpose

Peripheral Neuropathy

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
venlafaxine
placebo
questionnaire administration
quality-of-life assessment
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Peripheral Neuropathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (management of therapy complications)

Arm II (placebo)

Arm Description

Patients receive venlafaxine PO BID beginning on day 1 of and continuing through completion of FOLFOX.

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

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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)
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.

Full Information

First Posted
May 31, 2012
Last Updated
September 4, 2019
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT01611155
Brief Title
Venlafaxine in Preventing Chronic Oxaliplatin-Induced Neuropathy In Patients Receiving Combination Chemotherapy
Official Title
A Pilot Randomized, Placebo-controlled, Double Blind Study of Venlafaxine to Prevent Oxaliplatin-Induced Neuropathy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 17, 2012 (Actual)
Primary Completion Date
March 7, 2014 (Actual)
Study Completion Date
September 23, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Neuropathy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (management of therapy complications)
Arm Type
Experimental
Arm Description
Patients receive venlafaxine PO BID beginning on day 1 of and continuing through completion of FOLFOX.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO BID beginning on day 1 of and continuing through completion of FOLFOX.
Intervention Type
Drug
Intervention Name(s)
venlafaxine
Other Intervention Name(s)
Effexor, VNF
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 2 weeks
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Up to 2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Loprinzi
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26248652
Citation
Zimmerman C, Atherton PJ, Pachman D, Seisler D, Wagner-Johnston N, Dakhil S, Lafky JM, Qin R, Grothey A, Loprinzi CL. MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy. Support Care Cancer. 2016 Mar;24(3):1071-8. doi: 10.1007/s00520-015-2876-5. Epub 2015 Aug 8.
Results Reference
derived

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

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