Peripheral Neuropathy
Conditions
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.
Interventions
DRUGvenlafaxine
Given PO
DRUGplacebo
Given PO
OTHERquestionnaire administration
Ancillary studies
OTHERquality-of-life assessment
Ancillary studies
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Venlafaxine) Patients receive venlafaxine PO BID beginning on day 1 of and continuing through completion of FOLFOX. | 24 |
| Arm II (Placebo) Patients receive placebo PO BID beginning on day 1 of and continuing through completion of FOLFOX. | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Alternative treatment | 0 | 1 |
| Overall Study | Disease progression | 1 | 0 |
| Overall Study | Ineligible patient | 0 | 1 |
| Overall Study | Refused further treatment | 6 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (Venlafaxine) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 11.3 | 58.4 years STANDARD_DEVIATION 10.3 | 60.3 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 24 | 1 / 25 |
| other Total, other adverse events | 21 / 24 | 20 / 25 |
| serious Total, serious adverse events | 2 / 24 | 2 / 25 |
Outcome results
Primary
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.
Time frame: Up to 2 weeks
Population: Patients who completed the (QLQ)-CIPN20 Sensory neuropathy items at cycle 1 are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Venlafaxine) | 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 | 96.22 score on a scale | Standard Deviation 5.88 |
| Arm II (Placebo) | 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 | 95.83 score on a scale | Standard Deviation 8.84 |
p-value: 0.87t-test, 2 sided
Secondary
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.
Time frame: Up to 2 weeks
Population: There were a few Venlafaxine patients who completed the items for the motor subscale but did not complete the items for autonomic subscale in cycle 1 and thus the number analyzed for each subscale is different on the venlafaxine arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Venlafaxine) | 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) | Motor subscale | 97.28 score on a scale | Standard Deviation 6.33 |
| Arm I (Venlafaxine) | 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) | Autonomic subscale | 91.36 score on a scale | Standard Deviation 15.03 |
| Arm II (Placebo) | 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) | Motor subscale | 95.98 score on a scale | Standard Deviation 6.82 |
| Arm II (Placebo) | 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) | Autonomic subscale | 90.74 score on a scale | Standard Deviation 12.34 |
Comparison: Motor subscalep-value: 0.53t-test, 2 sided
Comparison: autonomic subscalep-value: 0.89t-test, 2 sided