Breast Cancer, Colorectal Cancer, Lung Cancer, Prostate Cancer, Tobacco Use Disorder
Conditions
Keywords
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
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.
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.
Interventions
DRUGmemantine 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.
DRUGplacebo
Placebo by mouth through completion of 12 weeks.
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention | 12 weeks | Retention is defined as the percentage of participants who complete the 12 week visit |
| Adherence | 12 weeks | Adherence is the percentage of prescribed pills taken while on therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Memantine 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. | 65 |
| Arm II - Placebo 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. | 65 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Multiple Reasons | 1 | 1 |
| Overall Study | Never Started | 9 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Toxicity | 7 | 5 |
| Overall Study | Withdrawal by Subject | 13 | 10 |
Baseline characteristics
| Characteristic | Arm I - Memantine | Arm II - Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 11 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 54 Participants | 100 Participants |
| Age, Continuous | 57 years | 56 years | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 64 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 53 Participants | 111 Participants |
| Region of Enrollment United States | 65 participants | 65 participants | 130 participants |
| Sex: Female, Male Female | 55 Participants | 55 Participants | 110 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 57 | 51 / 59 |
| serious Total, serious adverse events | 5 / 57 | 3 / 59 |
Outcome results
Primary
Adherence
Adherence is the percentage of prescribed pills taken while on therapy.
Time frame: 12 weeks
Population: Participants who returned pill diaries.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I - Memantine | Adherence | 86.0 percentage of prescribed pills |
| Arm II - Placebo | Adherence | 93.0 percentage of prescribed pills |
Primary
Retention
Retention is defined as the percentage of participants who complete the 12 week visit
Time frame: 12 weeks
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I - Memantine | Retention | 53.8 percentage of participants |
| Arm II - Placebo | Retention | 67.7 percentage of participants |
Secondary
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.
Time frame: 12 weeks
Population: Participants who reported any data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Memantine | Nicotine Dependence | 5.29 units on a scale | Standard Error 0.3 |
| Arm II - Placebo | Nicotine Dependence | 4.83 units on a scale | Standard Error 0.28 |
Secondary
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).
Time frame: 12 weeks
Population: Participants who provided data at any time
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Memantine | Smoking Withdrawal | 1.93 units on a scale | Standard Error 0.09 |
| Arm II - Placebo | Smoking Withdrawal | 2.01 units on a scale | Standard Error 0.08 |