Lung Carcinoma
Conditions
Brief summary
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
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.
Interventions
DRUGVarenicline
Given PO
DRUGPlacebo
Given PO
Complete counseling session
Sponsors
National Cancer Institute (NCI)
Pfizer
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Up to 30 days post-surgery | Number of patients that died within 30 days of surgery |
| Re-hospitalization | Up to 30 days post-surgery | Number of patients re-hospitalized within 30 days of surgery |
| Number of Paticipants With Incidence of Pulmonary Complications | Up to 24 weeks post-surgery | 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. |
| Number of Participants With Incidence of Intensive Care Unit Readmission | Up to 24 weeks post-surgery | 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. |
| Number of Participants With Incidence of Unspecified Wound Infection | Up to 24 weeks post-surgery | 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. |
| Number of Participants With Incidence of Anastomotic Failure | Up to 24 weeks post-surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence Rates as Measured by Self-report | Up to 12 weeks | — |
| Change in QOL as Measured by the LASA-12, PHQ-9, SEQ-12 | Baseline up to 24 weeks after surgery | Analysis of covariance and linear mixed model repeated measures analysis will be used for each assessment domain (LASA-12, PHQ-9, SEQ12). |
| Smoking Abstinence Rates as Measured by Salivary Cotinine Testing | Up to 12 weeks | — |
| Change in QOL as Measured by Was It Worth It Assessments | At 12 weeks after surgery | — |
| Length of Hospital Stay | The time from surgery until the patient is released from the hospital | Logrank testing of Kaplan-Meier estimates will be used for length of hospital stay and supplemented by Cox models to control for concomitant covariates. |
| Length of High Dependency Unit Stay | The time from surgery until the patient is released from the hospital | 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. |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) 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.\> \> Varenicline: Given PO\>
\> Tobacco Cessation Counseling: Complete counseling session | 12 |
| Control Group (Placebo and Behavioral Intervention) 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.\> \> Placebo: Given PO\>
\> Tobacco Cessation Counseling: Complete counseling session | 11 |
| Total | 23 |
Baseline characteristics
| Characteristic | Intervention Group (Varenicline and Behavioral Intervention) | Total | Control Group (Placebo and Behavioral Intervention) |
|---|---|---|---|
| Age, Continuous | 66.2 years STANDARD_DEVIATION 7.3 | 65.1 years STANDARD_DEVIATION 7.2 | 63.9 years STANDARD_DEVIATION 7.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 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 | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment United States | 12 participants | 23 participants | 11 participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 15 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 2 / 12 | 4 / 11 |
| serious Total, serious adverse events | 0 / 12 | 2 / 11 |
Outcome results
Primary
Mortality
Number of patients that died within 30 days of surgery
Time frame: Up to 30 days post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Mortality | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Mortality | 0 Participants |
Primary
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.
Time frame: Up to 24 weeks post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Number of Participants With Incidence of Anastomotic Failure | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Number of Participants With Incidence of Anastomotic Failure | 0 Participants |
Primary
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.
Time frame: Up to 24 weeks post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Number of Participants With Incidence of Intensive Care Unit Readmission | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Number of Participants With Incidence of Intensive Care Unit Readmission | 0 Participants |
Primary
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.
Time frame: Up to 24 weeks post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Number of Participants With Incidence of Unspecified Wound Infection | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Number of Participants With Incidence of Unspecified Wound Infection | 0 Participants |
Primary
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.
Time frame: Up to 24 weeks post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Number of Paticipants With Incidence of Pulmonary Complications | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Number of Paticipants With Incidence of Pulmonary Complications | 0 Participants |
Primary
Re-hospitalization
Number of patients re-hospitalized within 30 days of surgery
Time frame: Up to 30 days post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group (Varenicline and Behavioral Intervention) | Re-hospitalization | 0 Participants |
| Control Group (Placebo and Behavioral Intervention) | Re-hospitalization | 0 Participants |
Secondary
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).
Time frame: Baseline up to 24 weeks after surgery
Secondary
Change in QOL as Measured by Was It Worth It Assessments
Time frame: At 12 weeks after surgery
Secondary
Change in QOL as Measured by Was It Worth It Assessments
Time frame: At 24 weeks after surgery
Secondary
Expanded Complication Rate
Time frame: Up to 1 year
Secondary
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.
Time frame: The time from surgery until the patient is released from the hospital
Secondary
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.
Time frame: The time from surgery until the patient is released from the hospital
Secondary
Smoking Abstinence Rates as Measured by Salivary Cotinine Testing
Time frame: Up to 12 weeks
Secondary
Smoking Abstinence Rates as Measured by Self-report
Time frame: Up to 12 weeks
Secondary
Treatment Adherence Rates Related to Visits, Medication Compliance, Quitline Usage, and Surgeon Teachable Moment Delivery
Time frame: Up to 12 weeks