Management of Tobacco Treatment Intervention in Reducing Surgical Complications in Patients With Newly Diagnosed Lung Cancer Who Smoke Cigarettes

Study Overview
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Brief Summary
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This randomized phase III trial studies how well management of a tobacco treatment intervention works in reducing surgical complications in patients with newly diagnosed lung cancer who smoke cigarettes. Management of a tobacco treatment intervention compares varenicline (a drug that reduces the craving and withdrawal symptoms that occur with abstinence from nicotine) and behavioral interventions (consisting of a brief clinician-delivered intervention and tobacco quitline [tobacco cessation service available through a toll-free telephone number] follow-up) with placebo (a pill with no active medication) along with similar behavioral interventions. It is not yet known whether management of a tobacco treatment intervention is more effective in reducing surgical complications than placebo.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if varenicline plus a behavioral intervention consisting of a brief clinician-delivered intervention and tobacco quitline follow-up, decreases postsurgical complications through 24 weeks after surgery when compared to placebo plus the behavioral intervention in lung cancer patients who undergo surgery and are motivated to stop smoking. SECONDARY OBJECTIVES: I. To compare changes from baseline to 12 and 24 weeks after surgery in the patient quality of life (Linear Analogue Self-Assessment [LASA]-12) domains between the intervention (varenicline) and control group (placebo). II. To compare changes from baseline to 6, 12 and 24 weeks after surgery in the patient quality of life related domains (LASA) for the Patient Health Questionnaire (PHQ)-9 and Smoking Self Efficacy Questionnaire (SEQ)12 between the intervention and control groups. III. To compare the proportion of patients 12 weeks and 24 weeks after surgery who endorse (Was It Worth It) each treatment (intervention versus [vs] control groups). IV. To compare post-operative care (as measured by length of hospital and high dependency unit stay) between the intervention and control groups. V. To compare treatment adherence between the intervention and control groups. VI. To compare rates of smoking abstinence between the intervention and control groups as a covariate of the primary outcome only.

Official Title
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Reducing Surgical Complications in Newly Diagnosed Lung Cancer Patients Who Smoke Cigarettes

Conditions
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Lung Carcinoma

Intervention / Treatment
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* Drug: Varenicline
* Drug: Placebo
* Other: Tobacco Cessation Counseling


Participation Criteria
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Eligibility Criteria
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Eligible patients will have a new diagnosis of lung cancer and have sought a surgical consult relating to this diagnosis Surgery must be scheduled no sooner than 10 days after randomization and no more than twelve weeks after randomization Have smoked daily or nearly every day in the previous 6 months up to the date of surgical consult AND have smoked at least one puff in the previous 7 days Motivated to stop smoking, as indicated by a score of 6 or above on the Contemplation Ladder Within the 30 days before registration, no use of: 1) any pharmacologic treatment for smoking cessation, including bupropion or nicotine replacement therapy; 2) any nicotine delivery system (i.e., e-cigarettes and vape products); or 3) be enrolled in any formal behavioral treatment program for tobacco dependence as determined by patient report No allergies to and not currently using varenicline No suicidal thoughts as indicated by a positive (1+) response to the PHQ9 No active untreated clinically significant psychiatric condition (psychosis, bipolar disorder, or depression) Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) No unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia No history of seizures No unstable neurologic, hepatic, renal, cardiovascular, lymphatic, or metabolic disease Not currently on renal dialysis or has a history of significant renal impairment No recent history (=< 90 days) of substance abuse (outside of tobacco) defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) as: If male, drinking > 14 alcoholic beverages per week for past 1 month If female, drinking > 7 alcoholic beverages per week for past 1 month Use of cocaine, heroin, club drugs (i.e., 3,4-methylenedioxymethamphetamine (MDMA)/ecstasy), methamphetamine, or hallucinogens (e.g., lysergic acid diethylamide [LSD]) at any time during the past 1 month Use of marijuana on a weekly basis for the past 1 month Patients must be able to complete study questionnaires in English No other household member or relative participating in the study No known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder study adherence Calculated creatinine clearance >= 30 mL/min * For females, use 85% of calculated creatinine clearance (CrCl) value

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group (varenicline and behavioral intervention)<br>Patients receive varenicline PO QD on days 1-3 and BID on days 4-84 for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also complete behavioral intervention consisting of no smoking message from surgical team member and how to use NCI quitline at surgical consult. | Drug: Varenicline<br>* Given PO<br>Other: Tobacco Cessation Counseling<br>* Complete counseling session<br>|
| Placebo Comparator: Control group (placebo and behavioral intervention)<br>Patients receive placebo PO QD on days 1-3 and BID on days 4-84 for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also complete behavioral intervention consisting of no smoking message from surgical team member and how to use NCI quitline at surgical consult. | Drug: Placebo<br>* Given PO<br>Other: Tobacco Cessation Counseling<br>* Complete counseling session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Number of patients that died within 30 days of surgery | Up to 30 days post-surgery | 
| Re-hospitalization | Number of patients re-hospitalized within 30 days of surgery | Up to 30 days post-surgery | 
| Number of Paticipants With Incidence of Pulmonary Complications | Surgical complication incidence rates at 24 weeks after surgery will be compared between the intervention vs. control groups using a Fisher's exact test. Logistic regression models will supplement the univariate analysis, using complication incidence as the dependent variable and will include smoking status at the time of surgery as an independent variable and also adjust for age, gender, Fagerström Test for Nicotine Dependence (FTND), time between randomization and surgery, and presence of adjuvant chemotherapy and/or radiation therapy. We will also explore the collinear relationship between arm and smoking status to see whether they can be included together in the logistic models. | Up to 24 weeks post-surgery | 
| Number of Participants With Incidence of Intensive Care Unit Readmission | Surgical complication incidence rates at 24 weeks after surgery will be compared between the intervention vs. control groups using a Fisher's exact test. Logistic regression models will supplement the univariate analysis, using complication incidence as the dependent variable and will include smoking status at the time of surgery as an independent variable and also adjust for age, gender, FTND, time between randomization and surgery, and presence of adjuvant chemotherapy and/or radiation therapy. A separate logistic model will be created including treatment arm instead of smoking status. We will also explore the collinear relationship between arm and smoking status to see whether they can be included together in the logistic models. | Up to 24 weeks post-surgery | 
| Number of Participants With Incidence of Unspecified Wound Infection | Surgical complication incidence rates at 24 weeks after surgery will be compared between the intervention vs. control groups using a Fisher's exact test. Logistic regression models will supplement the univariate analysis, using complication incidence as the dependent variable and will include smoking status at the time of surgery as an independent variable and also adjust for age, gender, FTND, time between randomization and surgery, and presence of adjuvant chemotherapy and/or radiation therapy. A separate logistic model will be created including treatment arm instead of smoking status. We will also explore the collinear relationship between arm and smoking status to see whether they can be included together in the logistic models. | Up to 24 weeks post-surgery | 
| Number of Participants With Incidence of Anastomotic Failure | Surgical complication incidence rates at 24 weeks after surgery will be compared between the intervention vs. control groups using a Fisher's exact test. Logistic regression models will supplement the univariate analysis, using complication incidence as the dependent variable and will include smoking status at the time of surgery as an independent variable and also adjust for age, gender, FTND, time between randomization and surgery, and presence of adjuvant chemotherapy and/or radiation therapy. A separate logistic model will be created including treatment arm instead of smoking status. We will also explore the collinear relationship between arm and smoking status to see whether they can be included together in the logistic models. | Up to 24 weeks post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QOL as Measured by the LASA-12, PHQ-9, SEQ-12 | Analysis of covariance and linear mixed model repeated measures analysis will be used for each assessment domain (LASA-12, PHQ-9, SEQ12). | Baseline up to 24 weeks after surgery | 
| Change in QOL as Measured by Was It Worth It Assessments |  | At 12 weeks after surgery | 
| Change in QOL as Measured by Was It Worth It Assessments |  | At 24 weeks after surgery | 
| Length of Hospital Stay | Logrank testing of Kaplan-Meier estimates will be used for length of hospital stay and supplemented by Cox models to control for concomitant covariates. | The time from surgery until the patient is released from the hospital | 
| Length of High Dependency Unit Stay | Logrank testing of Kaplan-Meier estimates will be used for length of high dependency unit stay and supplemented by Cox models to control for concomitant covariates. | The time from surgery until the patient is released from the hospital | 
| Expanded Complication Rate |  | Up to 1 year | 
| Treatment Adherence Rates Related to Visits, Medication Compliance, Quitline Usage, and Surgeon Teachable Moment Delivery |  | Up to 12 weeks | 
| Smoking Abstinence Rates as Measured by Self-report |  | Up to 12 weeks | 
| Smoking Abstinence Rates as Measured by Salivary Cotinine Testing |  | Up to 12 weeks |