A Pilot Randomized, Placebo-controlled, Double Blind Study of Venlafaxine to Prevent Oxaliplatin-Induced Neuropathy
18 Years
N/A
Both
Peripheral Neuropathy
Trial Information
A Pilot Randomized, Placebo-controlled, Double Blind Study of Venlafaxine to Prevent Oxaliplatin-Induced Neuropathy
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.
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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Outcome Measure:
Chronic, cumulative neurotoxicity associated with oxaliplatin during the treatment course as measured by the sensory subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20
Outcome 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. 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. Linear mixed models or GEE modeling will be applied, whichever is applicable, based upon available data. The 95% confidence intervals will be constructed for the mean difference in sensory neuropathy score between arms.
Outcome Time Frame:
6 months
Safety Issue:
Yes
Principal Investigator
Charles Loprinzi
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
MC11C4
NCT ID:
NCT01611155
Start Date:
February 2012
Completion Date:
Related Keywords:
- Peripheral Neuropathy
- Peripheral Nervous System Diseases
- Demyelinating Diseases
- Polyneuropathies
- Nerve Compression Syndromes
- Neurologic Manifestations
- Neurotoxicity Syndromes
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
