Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Lung Neoplasms

Hematoma, Subdural

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All trial participants will receive smoking cessation counseling (standard of care) and will be given the AHRQ "Is Lung Cancer Screening Right for me?" patient decision aid to review independently while in the hospital.

In addition to the smoking cessation counseling and decision aid received by all subjects, intervention subjects will receive shared decision making (SDM) + CHW navigation.

All participants will receive inpatient smoking cessation counseling by the tobacco-trained NP. Inpatient smoking cessation counseling is the standard of care at BMC.

Smoking Cessation Counseling

The AHRQ "Is Lung Cancer Screening Right for me?" patient decision aid is a 4-page paper format with the following features: 1) LDCT screening harms and benefits information, written in plain language and using pictographs, easily understood by those with low health literacy; 2) prompts to clarify patient values and preferences and to stimulate discussion about tradeoffs; 3) clear quit smoking messaging and resources (1-800-QUIT-NOW)

Decision Aid

During the smoking cessation consultation, the nurse practitioner (NP) will conduct SDM, using the 4-page AHRQ "Is Lung Cancer Screening Right for me?" decision aid as a guide. The purpose of SDM is three-fold: 1) conduct a tailored discussion on tradeoffs of LDCT screening, consistent with Centers for Medicare \& Medicaid Services (CMS) requirements for SDM using a decision aid; 2) directly connect interested patients to LDCT screening; 3) to empower and motivate patients to quit smoking within the LDCT screening context.

Shared decision making (SDM)

The CHW will meet with the participant after the SDM to initiate the coordination of outpatient tobacco treatment, referral to LCS, and resources to address the barriers to preventive services. The CHW will follow patients subjects in the intervention arm for 3 months to help navigate and address negative social determinants of health that are barriers to LCS and tobacco treatment. For patients who agree to screening, the CHW will schedule the appointment, arrange the transportation to appointment, and meet participant at the appointment to facilitate the screening.

CHW Navigation

Hasmeena Kathuria, MD

Lung cancer suffers from large racial and socioeconomic disparities. Yet those at the highest risk of lung cancer death - current smokers, blacks, and individuals with low socioeconomic status (SES) and negative social determinants of health (SDH) - are less likely to receive preventive health services, including the two most effective interventions to reduce lung cancer mortality: tobacco dependence treatment and lung cancer screening (LCS) with low-dose computed tomography (LDCT). At Boston Medical Center (BMC) these preventive services are grossly underutilized, in part due to barriers our patients face in accessing these outpatient programs. Innovative approaches are needed to guide high-risk smokers to post-discharge early lung cancer detection services.

The overarching goal of this study is to reduce disparities in lung cancer morbidity and mortality by using hospitalization at an urban safety net hospital as an opportunity to connect high-risk smokers to both LDCT lung cancer screening and tobacco dependence treatment.

In addition to inpatient shared decision making \[SDM\] by an NP using a decision aid, screen-eligible smokers will also be connected with a community health worker (CHW) to facilitate access to outpatient smoking cessation counseling and LCS (CHW navigation).

This study is a randomized controlled trial (RCT) among 128 hospitalized smokers at BMC (64 participants in each of two arms), to assess the effect of inpatient SDM + CHW Navigation (AHRQ LDCT screening decision aid + CHW + SDM discussion + smoking cessation counseling) compared to Enhanced Usual Care (smoking cessation counseling + decision aid) on LDCT screening completion at 3 months, patient knowledge, and smoking cessation at 6 months.

The research will meet two specific aims (SA1 and SA2).

SA1: To address barriers to engaging smokers in prevention and early detection of lung cancer, a pilot RCT (Pilot Study 2) will be conducted in which screen-eligible hospitalized smokers will be randomized to receive inpatient sdm + CHW navigation (inpatient SDM during smoking cessation counseling visits + CHW navigation to coordinate outpatient tobacco treatment, referral to LCS, and resources to address negative social determinant of health that present barriers to these preventive services) or Enhanced usual care (furnishing of LDCT screening decision aid during inpatient smoking cessation counseling visits). Compared to Enhanced Usual Care, it is hypothesized that inpatient sdm + CHW navigation will increase the number of patients completing LCS (1° outcome) and LCS knowledge, and biochemically validated smoking cessation at 6 months (2° outcome).

SA2: To collect stakeholder input to inform future implementation, Fifteen primary care providers (PCPs) will be interviewed to assess their impressions of the intervention, integration into workflow, and barriers to adoption. Fifteen smokers who received the intervention will be interviewed to learn their impressions of its utility and suggestions for improvement.

Inpatient Smokers and LDCT Screening Part 2

Engaging Low SES Inpatient Smokers in LDCT Lung Cancer Screening: Enhanced Interventions That Include CHWs to Address SDH Barriers

Data will be collected from the electronic health record (EHR) and the BMC lung cancer screening (LDCT) database.

Knowledge about LDCT screening will be measured with a 23-item instrument developed by Lau and colleagues and modified for a low health literacy population by Crothers. The instrument includes true/false and multiple choice questions that will be used to determine a total score representing knowledge of LDCT screening.

Participants will be asked during telephone interview if they are smoking.

Participants who self-report quitting will be invited to complete the CO test for biochemical verification. This dichotomous outcome will be defined by biochemically verified 7-day point prevalence abstinence at 6 months. At study end, participants will be identified as smokers who 1) self-report abstinence, but are identified as smokers via biochemical validation (CO level \>10 ppm), or 2) self-report abstinence, but refuse biochemical verification.

American Lung Association

Boston University

All Drugs and Chemicals

Varenicline

Nicotinic Agonists

Cholinergic Agents

Neurotransmitter Agents

Usual care included physician advice to quit smoking.

Intervention participants were provided with a cognitive-behavioral 12-week program consisting of varenicline (1mg bid, with initial titration up over week 1) and smoking cessation counseling targeted to the issues of thoracic cancer patients. We offered 7 counseling sessions but were flexible in offering additional counseling when needed. Counseling was delivered by a certified Tobacco Treatment Counselor using Motivational Interviewing (MI) techniques.

Median of 9 tobacco treatment counseling sessions conducted in person or by telephone.

Smoking cessation counseling

varenicline (1mg bid, with initial titration up over week 1) for 12 weeks

varenicline

Elyse Park, Ph.D.

The primary aim of the proposed study is to develop and assess the feasibility of delivering a smoking cessation intervention to patients undergoing lung surgery that begins before surgery and continues up to 3 months post-discharge. The secondary aim is to assess smoking cessation rates 3 months following surgery.

This is a pilot study evaluating the feasibility of a cognitive-behavioral smoking cessation plus Varenicline program, designed specifically for early stage lung cancer patients and patients with a potential lung cancer diagnosis pre and post-surgery. The study population will be approximately 80 smokers who have upcoming lung resection surgery scheduled at Massachusetts General Hospital (MGH) in Boston. A patient will be considered eligible for the intervention or control group if he or she 1) is scheduled for a lung resection surgery with either a lung cancer diagnosis or a potential lung cancer diagnosis, and 2) had a cigarette in the past 2 weeks, 3) is willing to make a pre-surgical quit attempt. Patients will be excluded from the control group if they are 1) non-English speaking, 2) determined medically ineligible by their surgeon/oncologist, 3) suffering from psychosis or dementia 4) is currently on Varenicline has been on Varenicline for more than 3 weeks, or 5) is otherwise unable to participate in the intervention. Patients will be excluded from the intervention group if they are 1) non-English speaking, 2) determined medically ineligible by their surgeon, 3) suffering from psychosis or dementia 4) have been taking Varenicline for longer than three weeks 5) have been taking Bupropion (for smoking cessation purposes) for more than three weeks, 6) is otherwise unable to participate in the intervention.

Smoking Cessation Intervention for Thoracic Patients

A Pilot Smoking Cessation Study for Newly Diagnosed Lung Cancer Patients

Number of participants who completed the 12-week follow-up survey and thus the study.

7-day point prevalence abstinence ("Have you smoked a cigarette, even a puff, in the past 7 days?") was assessed at 12-week follow-up. Self reported abstinence was confirmed only if a salivary cotinine level was \< 15 ng/ml or an expired carbon monoxide measurement was \<10 ppm.

National Cancer Institute (NCI)

Massachusetts General Hospital

Elyse Park, PhD, Principal Investigator

Control

12-week program consisting of varenicline (1mg bid, with initial titration up over week 1) and smoking cessation counseling sessions targeted to the issues of thoracic cancer patients.

Intervention

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The generalizability of the findings are limited by a single study site. The statistical power to detect differences was limited by the small sample size of this pilot study.

Elyse Park, Ph.D., MPH

Determination of the Feasibility of a Cognitive Behavioral Smoking Cessation Intervention.

46 participants (32 intervention, 14 control) returned a cotinine confirmation kit for biochemical validation of 7 day point prevalent tobacco abstinence at 12 weeks. 3 control participants were excluded from the follow-up analysis.

Biochemically-validated 7-day Point Prevalence Tobacco Abstinence

Intervention participants were provided with a 12-week program consisting of varenicline (1mg bid, with initial titration up over week 1) and smoking cessation counseling targeted to the issues of thoracic cancer patients. We had proposed to offer 7 counseling sessions but were flexible in offering additional sessions when needed. The counseling was delivered by a certified Tobacco Treatment Counselor using motivational interviewing (MI) techniques.

Overall Study

Substance Related Disorders

Behaviors and Mental Disorders

Tobacco Use Disorder

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Nicotine

12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling

Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally

Days 85-168: Placebo - 1.0mg twice daily orally

24 weeks of active varenicline + smoking cessation counseling

Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally

Varenicline was used in accordance with FDA approved labeling: Day 1-Day 3 (0.5mg once daily); Day 4-Day 7 (0.5mg twice daily); and Day 8-Day 84 (1.0mg twice daily).

On Day 85, participants randomized to standard therapy will be given placebo pills (resembling the 1.0mg pills),

Placebo

Behavioral Counseling (from Week 0 - Week 18)

The counseling protocol was based on PHS guidelines for smoking cessation treatment (Fiore et al., 2008), used in our past studies with cancer patients (Schnoll et al., 2010a) and in our ongoing cessation trial at NU (R01 DA025078). Counseling is included given its efficacy at helping smokers quit (Fiore et al., 2008) and to increase study retention. Counseling is provided to both treatment arms through Week 18 to equate for time and attention across arms and since this method was used in varenicline clinical trials (Gonzales et al., 2006) and in our extended therapy trial (Schnoll et al., 2010b). In-person counseling was selected for most sessions to ensure adequate monitoring of participant safety and adherence throughout the trial.

Robert A Schnoll, PhD

Upwards of 33-50% of cancer patients who smoked prior to diagnosis continue to smoke following diagnosis and treatment. With medical advances in cancer care yielding a growing constituency of cancer survivors, addressing nicotine dependence in this population is a priority. While PHS guidelines recommend acute treatment durations with approved medications for tobacco use, extending the duration of treatment beyond the standard treatment duration significantly increases quit rates, reduces the risk for a relapse, and promotes recovery to abstinence following a lapse. Varenicline may be particularly effective for cancer patients given the drug's beneficial effects on affect and cognition. In this trial, 374 cancer patients will be randomized to standard varenicline treatment (12 weeks active + 12 weeks placebo) or extended varenicline treatment (24 weeks active). The investigators hypothesize that 1) Extended varenicline therapy will increase 24- and 52-week biochemically-confirmed abstinence versus standard varenicline treatment, 2) Quality of life will be rated higher in the extended therapy group versus the standard therapy group, and there will be no significant differences between groups in terms of severe side effects, and 3) Improved affect and reduced cognitive impairment will mediate the effect of extended therapy on quit rates.

BACKGROUND

Prevalence of Smoking among Cancer Patients

The rate of smoking among individuals with cancer who are age 40 or under are substantially higher (38-40%) than rates of smoking in the comparable age group in the general population (\~26%; Bellizzi et al., 2005; Coups \& Ostroff, 2005). Studies with patients that have traditional tobacco-related cancers show extremely high rates of smoking; upwards of 50% of head and neck (Duffy et al., 2008) and lung (Cooley et al., 2009) cancer patients report current smoking. However, high rates of smoking are not unique to such traditional tobacco-related disease sites. Significant rates of current smoking have been reported among testicular (19%; Shinn et al., 2007), prostate (16-17%; Gong et al., 2008; Pantarotto et al., 2007), cervical (21%; Beesley et al., 2008), breast (19%; Li et al., 2009), bladder (18%; Blanchard et al., 2008), esophageal (39%; Sundelof et al., 2008), colorectal (22%; Vincenzi et al., 2009), and lymphoma (19%; Geyer et al., 2010) cancer patients. Overall, about one-third to one-half of cancer patients who were smokers prior to their diagnosis continue to smoke following diagnosis (Gritz et al., 2006).

Adverse Health Consequences of Smoking among Individuals with Cancer

Continued smoking by cancer patients has been associated with diminished QOL, reduced survival probability and duration, and increased risk for disease recurrence and a second primary tumor (Gritz et al., 2006; 2007). Continued smoking by cancer patients is associated with greater treatment side effects or diminished QOL among head and neck (Duffy et al., 2007; Zevallos et al., 2009), lung (Daniel et al., 2009), prostate (Ku et al., 2009), and a heterogeneous group of (Schnoll et al., 2010a) cancer patients. A recent meta-analysis of studies with lung cancer patients found that continued smoking was associated with an increased risk of death, recurrence, and a second primary tumor (Parsons et al., 2010). Likewise, studies with head and neck cancer patients have reported that patients who continue to smoke following their diagnosis have a lower survival rate and an increased risk for a recurrence and a second primary tumor (Browman et al., 2002; Hilgert et al., 2009; Fortin et al., 2009; Leon et al., 2009). Continued smoking has also been associated with reduced survival among breast (Aksoy et al., 2007), lymphoma (Geyer et al., 2010), esophageal (Sundelof et al., 2008), prostate (Gong et al., 2008), cervical (Coker et al., 2009), and bladder (Aveyard et al., 2002) cancer patients and with an increased risk of recurrence or a second primary tumor among bladder (Fleshner et al., 1999), breast (Li et al., 2009), lymphoma (Moser et al., 2006), and colorectal (Jacobson et al., 1994) cancer patients. Continued smoking may worsen prognosis by reducing the effectiveness of chemotherapy (Duarte et al., 2008; van der Bol et al., 2007; Vincenzi et al., 2009; Hotta et al., 2008) and radiotherapy (Browman et al., 1993).

Nicotine Dependence Treatments for Those with Cancer

Very few smoking cessation trials have been conducted with this population (Gritz et al., 2006; 2007) and many of these past trials have used small samples and relied on self-report for smoking abstinence outcomes (de Moor et al., 2008). After nearly two decades of research in this area, not a single smoking cessation randomized clinical trial has yielded significant treatment effects (excluding Emmons et al., 2009, which studied adult survivors of childhood cancer; de Moor et al., 2008). Nurse-led (Griebel et al., 1998; Stanislaw \& Wewers, 1994; Wewers et al., 1994), physician-led (Browning et al., 2000; Gritz et al., 1993; Schnoll et al., 2003b), and behavioral (Schnoll et al., 2005; Wakefield et al., 2004) smoking cessation trials have failed to yield treatment effects for cancer patients. Our recent clinical trial with bupropion (Schnoll et al., 2010a) found no main effect for the medication, but bupropion increased abstinence rates, reduced withdrawal symptoms, and improved QOL more for patients with depression, vs. those without depression. Lastly, a very recent varenicline study reported end-of-treatment quit rates of 34%, vs. 14% for the comparison group (OR = 3.14), and a side effect profile that mirrored the general population (Park et al., 2011). While these data are encouraging, as were reported feasibility data, the study was under-powered (n = 49) and did not use a randomized design. Thus, there is currently no empirically-based treatment model for addressing nicotine dependence in the oncologic context. As such, a recent NCI meeting, with representatives from NCI cancer centers, concluded that the evaluation of novel smoking cessation interventions for cancer patients is a critical priority (Morgan et al., 2010).

A Novel Treatment for Cancer Patients who Smoke: Extended Duration Varenicline Thus, nicotine dependence treatments for cancer patients may show greater efficacy if they adequately address the patient's relatively high level of nicotine dependence, risk for psychological distress and cognitive impairment, and delayed relapse process. We hypothesize that extended duration varenicline (24-weeks) will address these barriers to cessation and significantly increase quit rates, vs. standard varenicline treatment (12 weeks).

Our rationale for selecting varenicline is as follows. First, the high rate of nicotine dependence among cancer patients underscores the need to include a pharmacotherapy as part of treatment. Varenicline is currently the most efficacious FDA-approved medication for nicotine dependence, yielding quit rates that significantly exceed those produced by bupropion (Gonzales et al., 2006; Jorenby et al., 2006) and nicotine patch (Aubin et al., 2008; Biazzo et al., 2010; Stapleton et al., 2008). Second, varenicline mitigates adverse psychological effects and cognitive impairment associated with quitting smoking (Patterson et al., 2009; Smith et al., 2009; Philip et al., 2009; Rollema et al., 2009; Sofuoglu et al., 2009). The anti-depressant-like (Rollema et al., 2009) and cognitive enhancing (Loughead et al., 2010) effects of varenicline is consistent with what we know about how varenicline works. As a nicotinic acetylcholine receptor (nAChRs) partial agonist, varenicline binds to nAChRs and blocks the entry of nicotine (from smoking) into the receptor and stimulates a moderate release of dopamine. This reduces the rewarding effects of smoking and reduces withdrawal symptoms (Rollema et al., 2009). Preclinical studies also indicate that α4β2 nAChRs subtypes are critical for cognition (Levin et al., 2006) and stimulation of these receptors by varenicline yields improved cognitive function (Loughead et al., 2010). Likewise, animal studies indicate that the simultaneous activation and desensitization of nAChRs receptors produced by nicotinic partial agonists like varenicline can yield antidepressant-like effects (Mineur \& Picciotto, 2010), which underlies current evaluations of varenicline as a treatment for major depression. Third, varenicline is efficacious and safe for treating nicotine dependence among various clinical populations, including: cardiovascular disease patients (Rigotti et al., 2010), COPD patients (Tashkin et al., 2010), smokers with comorbid alcohol (Hays et al., 2010) and cocaine (Poling et al., 2010) dependence, and smokers with comorbid affective or psychotic disorders (McClure et al., 2010; Smith et al., 2009; Philip et al., 2009). It has been shown to be safe when taken over 52 weeks (Williams et al., 2007). Although there have been reports of adverse psychiatric events following varenicline use, leading the FDA to mandate a boxed warning for varenicline, pooled data from controlled efficacy trials (Cahill et al., 2009; Tonstad et al., 2010), effectiveness trials (McClure et al., 2010), and large cohort studies (Gunnell et al., 2009; Kasliwal et al., 2009) demonstrate that varenicline is safe for treating nicotine dependence, even among smokers with psychiatric comorbidity, including depression (Stapleton et al., 2008; McClure et al., 2010; Steinberg et al., 2010).

Our rationale for selecting an extended duration treatment is as follows. First, we have shown, in a placebo-controlled randomized trial with general population smokers, that 24-weeks of transdermal nicotine, vs. the standard 8-weeks, increases 6-month quit rates by an OR of 1.81 (32% vs. 20%; Schnoll et al., 2010b). Second, and importantly, extending treatment with the nicotine patch to 24-weeks significantly helps smokers with high levels of nicotine dependence and cognitive impairment, in particular, to overcome their liability to relapse (see below). While extended therapy with transdermal nicotine did not offset the effect of depression symptoms on relapse rates, the quit rate among depressed smokers in extended treatment was almost 2-times higher than it was for depressed smokers in standard treatment (see below). Third, we showed in our placebo-controlled randomized clinical trial with general population smokers (Schnoll et al., 2010b) that extending treatment with transdermal nicotine to 24-weeks (vs. 8-weeks) significantly reduced the probability that smokers would experience a lapse and, importantly, increased the likelihood that smokers would recover to abstinence following a lapse. Extended duration treatment offered smokers who lapsed the opportunity to re-start their quit attempt and eventually achieve abstinence. Thus, extended duration varenicline may be particularly efficacious at addressing the barriers to cessation that are evident among cancer patients.

Extended Varenicline Treatment for Smoking Among Cancer Patients

Extended Duration Varenicline for Smoking Among Cancer Patients: A Clinical Trial

No smoking from baseline to time-point, after a 2-week grace period.

Number of Participants with Verified 7 Day Tobacco Abstinence.

The Short-Form Health Survey (SF-12) assesses Quality of Life (QOL). Scale range from 12 - 47. Higher score indicates worse quality of life.

University of Pennsylvania

Research staff member completed side effect assessments and determined the severity of the adverse events; the relationship of the event to the study drug and the decision on the course of action for the participant was decided by the site physicians and psychologists after review of the report. Participants were monitored for the development of adverse events by assessing side effects at each assessment time-point, as well as through open-ended questions during assessments.

12 weeks of active varenicline + 12 weeks of placebo + smoking cessation counseling

Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally

Days 85-168: Placebo - 1.0mg twice daily orally

Varenicline

Placebo

Smoking Cessation Counseling

Standard Varenicline Treatment

24 weeks of active varenicline + smoking cessation counseling

Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-168: 1.0mg twice daily orally

Varenicline

Smoking Cessation Counseling

Extended Varenicline Treatment

Age, Categorical

United States

Region of Enrollment

Scale range from 0-10. Higher score indicates greater nicotine dependence.

Fagerström Test for Nicotine Dependence

The Karnofsky Performance Scale is an assessment tool for functional impairment. Scale range from 0-100. Higher score indicates less functional impairment.

Karnofsky Performance Score

The ECOG Performance Scale is used to assess how a patient's cancer is progressing and assess how the disease affects the daily living abilities of the patient. Scale range from 0-5. Higher score indicates further progression of cancer.

ECOG Performance Status

Breath carbon monoxide is the level of carbon monoxide in a person's exhalation. The minimum score is 0, while there is no maximum score. Higher scores indicate a higher level of carbon monoxide in parts per million (ppm) in breath.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Inpatient Smokers and LDCT Screening Part 2	NCT03793894	Lung Cancer Scr... Smoking Cessati...	Smoking Cessati... Decision Aid Shared decision... CHW Navigation	55 Years - 80 Years	Boston University
Smoking Cessation Intervention for Thoracic Patients	NCT00580398	Lung Cancer	Smoking cessati... varenicline	-	Massachusetts General Hospital
Extended Varenicline Treatment for Smoking Among Cancer Patients	NCT01756885	Nicotine Depend...	Varenicline Placebo Smoking Cessati...	18 Years -	University of Pennsylvania

Spots Global Cancer Trial Database for smoking cessation counseling