Memantine Hydrochloride in Helping Cancer Survivors Stop Smoking

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01535040
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 130
• Location: 1
• Arms: 2
• Actual Duration (Months): 18
• Patients Per Site Per Month: 7.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Colorectal Cancer; Lung Cancer; Prostate Cancer; Tobacco Use Disorder	Drug: memantine hydrochloride; Drug: placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Randomized Placebo-Controlled Phase 2 Pilot Study of Memantine (Namenda) for Smoking Cessation Among Cancer Survivors
• Actual Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Retention [12 weeks]

   Retention is defined as the percentage of participants who complete the 12 week visit

2. Adherence [12 weeks]

   Adherence is the percentage of prescribed pills taken while on therapy.

Secondary Outcome Measures

1. Nicotine Dependence [12 weeks]

   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.

2. Smoking Withdrawal [12 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest Cancer Center CCOP Research Base	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Spangler, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01535040
• Other Study ID Numbers: IRB00020412; U10CA081851; REBACCCWFU 99311
• First Posted: Feb 17, 2012
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: cancer survivor; stage I non-small cell lung cancer; stage II non-small cell lung cancer; tobacco use disorder; stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage I prostate cancer; stage IIA prostate cancer; stage IIB prostate cancer; stage III prostate cancer; stage I colon cancer; stage IIA colon cancer; stage IIB colon cancer; stage IIC colon cancer; stage IIIA colon cancer; stage IIIB colon cancer; stage IIIC colon cancer; stage I rectal cancer; stage IIA rectal cancer; stage IIB rectal cancer; stage IIC rectal cancer; stage IIIA rectal cancer; stage IIIB rectal cancer; stage IIIC rectal cancer
• Additional relevant MeSH terms: Breast Neoplasms; Lung Neoplasms; Prostatic Neoplasms; Tobacco Use Disorder; Memantine

Study Results

Participant Flow

Arm/Group Title	Arm I - Memantine	Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
Period Title: Overall Study
STARTED	65	65
COMPLETED	35	44
NOT COMPLETED	30	21

Baseline Characteristics

Arm/Group Title	Arm I - Memantine	Arm II - Placebo	Total
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.	Total of all reporting groups
Overall Participants	65	65	130
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	46 70.8%	54 83.1%	100 76.9%
>=65 years	19 29.2%	11 16.9%	30 23.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	56	57
Sex: Female, Male (Count of Participants)
Female	55 84.6%	55 84.6%	110 84.6%
Male	10 15.4%	10 15.4%	20 15.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	65 100%	64 98.5%	129 99.2%
Unknown or Not Reported	0 0%	1 1.5%	1 0.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 1.5%	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 10.8%	11 16.9%	18 13.8%
White	58 89.2%	53 81.5%	111 85.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	65 100%	65 100%	130 100%

Outcome Measures

1. Primary Outcome

Title	Retention
Description	Retention is defined as the percentage of participants who complete the 12 week visit
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Arm I - Memantine	Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
Measure Participants	65	65
Number (95% Confidence Interval) [percentage of participants]	53.8 82.8%	67.7 104.2%

2. Primary Outcome

Title	Adherence
Description	Adherence is the percentage of prescribed pills taken while on therapy.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who returned pill diaries.

Arm/Group Title	Arm I - Memantine	Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
Measure Participants	48	52
Mean (Full Range) [percentage of prescribed pills]	86.0	93.0

3. Secondary Outcome

Title	Nicotine Dependence
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who reported any data

Arm/Group Title	Arm I - Memantine	Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
Measure Participants	64	65
Least Squares Mean (Standard Error) [units on a scale]	5.29 (0.30)	4.83 (0.28)

4. Secondary Outcome

Title	Smoking Withdrawal
Description	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).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who provided data at any time

Arm/Group Title	Arm I - Memantine	Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.	Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
Measure Participants	63	64
Least Squares Mean (Standard Error) [units on a scale]	1.93 (0.09)	2.01 (0.08)

Adverse Events

Time Frame	4 months (3 months of treatment and 1 month following the end of treatment)
Adverse Event Reporting Description	The sample size for this section is the number of participants who had post-randomization toxicity data recorded.
Arm/Group Title	Arm I - Memantine		Arm II - Placebo
Arm/Group Description	Participants receive memantine hydrochloride PO BID) on days 1-81 in the absence of unacceptable toxicity. 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.		Participants receive a placebo PO BID on days 1-81 in the absence of unacceptable toxicity. placebo: Placebo by mouth through completion of 12 weeks.
All Cause Mortality
	Arm I - Memantine		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I - Memantine		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/57 (8.8%)		3/59 (5.1%)
Cardiac disorders
Hypertension	1/57 (1.8%)	1	2/59 (3.4%)	7
Eye disorders
Retinal Tear	1/57 (1.8%)	2	0/59 (0%)	0
General disorders
Pain	1/57 (1.8%)	1	0/59 (0%)	0
Hepatobiliary disorders
Liver Dysfunction / Failure	0/57 (0%)	0	1/59 (1.7%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/57 (1.8%)	4	0/59 (0%)	0
Fracture	1/57 (1.8%)	1	0/59 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I - Memantine		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/57 (84.2%)		51/59 (86.4%)
Cardiac disorders
Hypertension	13/57 (22.8%)	31	13/59 (22%)	37
Ear and labyrinth disorders
Dizziness	16/57 (28.1%)	25	10/59 (16.9%)	22
Gastrointestinal disorders
Constipation	15/57 (26.3%)	31	13/59 (22%)	27
Diarrhea	6/57 (10.5%)	12	10/59 (16.9%)	15
Vomiting	3/57 (5.3%)	5	2/59 (3.4%)	2
General disorders
Fatigue	33/57 (57.9%)	83	25/59 (42.4%)	66
Headache	19/57 (33.3%)	33	19/59 (32.2%)	33
Somnolence	13/57 (22.8%)	23	8/59 (13.6%)	17
Musculoskeletal and connective tissue disorders
Back Pain	14/57 (24.6%)	54	12/59 (20.3%)	38
Psychiatric disorders
Confusion	10/57 (17.5%)	21	5/59 (8.5%)	9
Renal and urinary disorders
Renal and Urinary Disorder - Other	1/57 (1.8%)	1	5/59 (8.5%)	15
Respiratory, thoracic and mediastinal disorders
Cough	22/57 (38.6%)	69	27/59 (45.8%)	72
Dyspnea	16/57 (28.1%)	55	16/59 (27.1%)	40

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.