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

NCT ID: NCT01611155

Last Updated: 2019-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-17
• Study Completion Date: 2015-09-23

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.

Conditions

Peripheral Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Arm I (management of therapy complications)

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

Group Type: EXPERIMENTAL

venlafaxine

Intervention Type: DRUG

Given PO

questionnaire administration

Intervention Type: OTHER

Ancillary studies

quality-of-life assessment

Intervention Type: OTHER

Ancillary studies

Arm II (placebo)

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Given PO

questionnaire administration

Intervention Type: OTHER

Ancillary studies

quality-of-life assessment

Intervention Type: OTHER

Ancillary studies

Interventions

venlafaxine

Given PO

Intervention Type: DRUG

placebo

Given PO

Intervention Type: DRUG

questionnaire administration

Ancillary studies

Intervention Type: OTHER

quality-of-life assessment

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

Effexor; VNF; PLCB; quality of life assessment

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Loprinzi

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26248652 (View on PubMed)

Other Identifiers

NCI-2012-00318

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC11C4

Identifier Type: -

Identifier Source: org_study_id