Memantine Hydrochloride in Helping Cancer Survivors Stop Smoking

Randomized Placebo-Controlled Phase 2 Pilot Study of Memantine (Namenda) for Smoking Cessation Among Cancer Survivors

RATIONALE: Memantine hydrochloride may help people stop smoking by decreasing the symptoms of nicotine withdrawal.

PURPOSE: This randomized, pilot phase II trial studies how effective memantine hydrochloride works compared to placebo in helping cancer survivors stop smoking.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Colorectal Cancer; Tobacco Use Disorder; Lung Cancer; Prostate Cancer
• Intervention / Treatment: Drug: memantine hydrochloride; Drug: placebo

Detailed Description

OBJECTIVES:

Primary

• Estimate participation, accrual, adherence, and retention of cancer survivors who smoke and are randomized to receive memantine (memantine hydrochloride) (10 mg twice daily) or a matching placebo for 12 weeks.
• Estimate the self-reported abstinence rates of patients who are randomized to memantine or a matching placebo for 12 weeks and obtain a preliminary estimate of the treatment effect (difference in abstinence rates between the two groups).

Secondary

• Nicotine addiction will be assessed using the Wisconsin Inventory of Smoking Dependent Motives.
• Nicotine withdrawal will be measured by the Wisconsin Smoking Withdrawal Scale.
• Quality of life will be measured by the SF12 questionnaire.
• Toxicities will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.

OUTLINE: This is a randomized, placebo-controlled, pilot study. Participants are stratified according to gender (male vs female). Participants are randomized to 1 of 2 treatment arms.

• Arm I: Participants receive memantine hydrochloride orally (PO) twice daily (BID) on days 1-81 in the absence of unacceptable toxicity.
• Arm II: Participants receive placebo PO BID on days 1-81 in the absence of unacceptable toxicity.

Participants complete the Behavioral Risk Factor Surveillance Survey (BRFSS), the Self-reported Tobacco Abstinence, the Wisconsin Inventory of Smoking Dependent Motives, the Wisconsin Smoking Withdrawal Scale, SF-12 quality-of-life questionnaire, and the Fagerstrom Nicotine Tolerance Scale at baseline and every 2 weeks for 12 weeks during study.

Participants also undergo urine sample collection at weeks 4, 8, and 12 for cotinine test using the NicAlert test.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Cancer Center CCOP Research Base

Participation Criteria

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:

• Survivors of non-metastatic breast, prostate, or colorectal cancer, or stage I/II non-small cell lung cancer
• Age ≥ 18
• Smoked 100 tobacco cigarettes over lifetime at time of first interview, have smoked 10 or more cigarettes per day on most days over the past month
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky ≥ 70%)
• Ability to understand and the willingness to sign a written informed consent document
• Agrees to adhere to the study protocol and attend the required clinic visits
• Negative serum pregnancy test within 10 days prior to registration in women with child-bearing potential; women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Women who are currently breast-feeding are not eligible for this study

Exclusion Criteria:

• Use of chewing tobacco, pipe tobacco, snuff, or any other non-cigarette tobacco product is not allowed
• No patients with clinically significant uncontrolled medical conditions (e.g., unstable angina, myocardial infarction, transient ischemic attack [TIA], or cerebral vascular accident [CVA]) within past 3 months
• Creatinine ≥ 2 times upper limit of normal (ULN) in last six months
• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase (SGPT) ≥ 3 times ULN in last six months
• Current uncontrolled hypertension ≥ 160/90 mm Hg
• Excessive alcohol abuse defined as more than 5 drinks per day for men and 4 drinks per day for women
• Major medical or psychiatric illness which, in the opinion of the investigator, would prevent completion of treatment or would interfere with follow-up
• History of allergic reactions attributed to memantine

PRIOR CONCURRENT THERAPY:

• Six months post definitive treatment (except for ongoing hormonal or targeted therapies)
• Patients currently must not be taking Nicotine Replacement Therapy (NRT) and agree to not start NRT for the duration of the study
• Patients currently taking antidepressant or antianxiety medications must have been on a stable dose for 4 weeks prior to registration
• Patients currently receiving the following medications are not eligible: anticonvulsant agents (e.g., phenytoin, carbamazepine, gabapentin, etc.); antiparkinsonian agents (e.g., Levo Dopa, ropinirole); neuroleptic agents (e.g., risperidone, quetiapine); carbonic anhydrase inhibitors (e.g., Diamox® and Sequels®)
• Memantine should not be combined with other N-methyl d-aspartate (NMDA) antagonists (amantadine, ketamine, and dextromethorphan)
• Participants may not be receiving any other investigational agents
• No current use of illegal drugs or use of prescription medications for non-medical reasons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm I - Memantine; Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity.	Drug: memantine hydrochloride; Estimate participation, accrual, adherence, and retention of cancer survivors who smoke and are randomized to receive memantine (10 mg twice daily) or a matching placebo for 12 weeks.; Other Names: Memantine
PLACEBO_COMPARATOR: Arm II - Placebo; Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity.	Drug: placebo; Placebo by mouth through completion of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention	Retention is defined as the percentage of participants who complete the 12 week visit	12 weeks
Adherence	Adherence is the percentage of prescribed pills taken while on therapy.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Dependence	The Fagerstrom tolerance scale consists of 8 questions, each of which is scored on a 0 to 1 or 0 to 2 scale. The total score ranges from 0 to 11, with higher scores representing greater dependence.	12 weeks
Smoking Withdrawal	The Wisconsin Smoking Withdrawal Scale is a 28 item questionnaire that assesses nicotine withdrawal. It consists of seven subscales, each consisting of 3-5 questions all answered on a 0-4 scale. Subscale scores are the mean of the items comprising the scale. Some items are reverse scored. Higher scores indicate greater withdrawal symptoms. Subscales were scored if more than half the items were answered. A total score was calculated as the mean of the individual subscales (if more than half the subscales had scores).	12 weeks

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Spangler, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2012
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: February 14, 2012
• First Submitted That Met QC Criteria: February 14, 2012
• First Posted (ESTIMATE): February 17, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage III prostate cancer; stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage II breast cancer; stage IIIC breast cancer; cancer survivor; stage IA breast cancer; stage IB breast cancer; stage IIIB rectal cancer; stage IIIC rectal cancer; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer; stage I rectal cancer; stage I colon cancer; stage IIA colon cancer; stage IIB colon cancer; stage IIC colon cancer; stage IIIA colon cancer; stage IIA rectal cancer; stage IIB rectal cancer; stage IIC rectal cancer; stage IIIA rectal cancer; tobacco use disorder; stage IIIB colon cancer; stage IIIC colon cancer
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Breast Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: IRB00020412; U10CA081851 (U.S. NIH Grant/Contract); REBACCCWFU 99311 (OTHER: NCI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No