Memantine Hydrochloride in Helping Cancer Survivors Stop Smoking

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.

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