Tobacco Treatment Optimization and Preferences During Concurrent Cancer Treatment

Study Overview
=================
Brief Summary
-----------------
Smoking cessation has been shown to improve the effectiveness and reduce the morbidity of tobacco-related cancer treatments. We will identify effective smoking cessation strategies for patients who are receiving treatment for tobacco-related cancer. In this trial, patients' preferences in smoking cessation therapy will be the principal determinant by providers in developing a three component regimen of pharmaceutical therapy, counseling, and nicotine replacement therapy. This study will identify this cohort's preferences for smoking cessation strategies. We will then examine the impact of utilizing patient preferences upon cessation efficacy by directly comparing cessation success in this study with our recently completed study of the same population using the same tobacco treatments which were randomly assigned.

Detailed Description
-----------------
Background Cigarette smoking is associated with decreased survival and decreased efficacy of cancer therapy in those with smoking related malignancies. There is limited of study of smoking cessation for cancer patients being treated in regions with high tobacco use such as Kentucky. There is little study of cessation implementation in the community cancer treatment setting where the majority of cancer patients receive their cancer therapy. Most smokers have significant exposure to information and personal experience with tobacco treatments which, in some cases, leads to profound preferences. The effect of incorporating these patient preferences into tobacco treatment planning has not been studied or quantified. Study Design Phase II therapeutic clinical trial. Setting University of Kentucky Markey Cancer Center (MCC) and its affiliate research network of Community Cancer Centers (MCCRN) Methods Ninety-three subjects will be selected. All subjects will be active smoking oncology patients with a diagnosis of smoking related malignancy who are beginning a new course of therapy. In conjunction with their treating clinician, all subjects will be counseled and then select one of 12 cessation strategies. This will include a choice of continuous pharmacologic agent (veranicline, bupropion or transdermal nicotine patch), counseling strategy (11 session high intensity motivational based counseling or single session low intensity counseling), and whether or not to use as needed nicotine (gum, lozenges or spray). Data Analysis All subjects will be followed for six months. The primary endpoint will be a carbon monoxide monitoring confirmed negative seven-day point prevalence report of cessation at eight weeks. Data will then be analyzed and compared with a completed randomized clinical trial of the same treatment strategies in the same population of subjects where the cessation strategy was assigned (historical control). The proportion of subjects that have quit at week eight will be compared to the historical control proportion (namely, whether Ho:p=po vs Ha: p>po). This will be assessed using a z-score for a binomial proportion which will test whether the underlying proportion quitting at eight weeks (p) differs from the control proportion (po ranging from 0.215 to 0.26) estimated from our recently completed randomized trial of these same 12 cessation strategies.

Official Title
-----------------
Tobacco Treatment Optimization and Preferences During Concurrent Cancer Treatment

Conditions
-----------------
Smoking Cessation, Cancer, Treatment-Related

Intervention / Treatment
-----------------
* Drug: Varenicline
* Drug: Bupropion
* Drug: Long-acting nicotine replacement therapy
* Behavioral: Low-intensity counseling
* Behavioral: High-intensity counseling
* Other: No nicotine replacement therapy
* Drug: Nicotine Replacement Products


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: newly diagnosed or recurrent tobacco related malignancy smoked at least 1 cigarette within 4 weeks of study enrollment 10-pack year history of cigarette smoking smoked at least 1 cigarette within 1 month of cancer diagnosis life expectancy greater than 1 year Exclusion Criteria: allergy to buproprion, varenicline and transdermal medicine history of suicide attempt hospitalized for psychiatric illness within past 2 years history of active or uncontrolled eating disorder uncontrolled epilepsy or seizure disorder pregnant or lactating within 3 months of myocardial infarction unstable angina uncontrolled hypertension serious arrhythmia history of taking varenicline or buproprion within one month of enrollment concurrent enrollment in tobacco cessation therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This trial is a parallel design. However, it is part of a broader sequential cohort design to compare the effects of preference driven tobacco treatment upon cessation versus effects of a previous cohort from a separate randomized controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Varenicline, Intense Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive varenicline, counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Varenicline<br>* Varenicline therapy will be 12-week course. On days 1-3 participants will receive 0.5mg once daily; days 4-7 receive 0.5mg twice daily and day 8 until the end of treatment receive 1mg twice daily.<br>* Other names: Chantix;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group : Varenicline, Intense Counselling<br>Patients diagnosed with tobacco-related treatment will receive varenicline and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Varenicline<br>* Varenicline therapy will be 12-week course. On days 1-3 participants will receive 0.5mg once daily; days 4-7 receive 0.5mg twice daily and day 8 until the end of treatment receive 1mg twice daily.<br>* Other names: Chantix;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 3: Varenicline, Minimal Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive varenicline, counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Varenicline<br>* Varenicline therapy will be 12-week course. On days 1-3 participants will receive 0.5mg once daily; days 4-7 receive 0.5mg twice daily and day 8 until the end of treatment receive 1mg twice daily.<br>* Other names: Chantix;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 4: Varenicline, Minimal Counselling<br>Patients diagnosed with tobacco-related treatment will receive varenicline and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Varenicline<br>* Varenicline therapy will be 12-week course. On days 1-3 participants will receive 0.5mg once daily; days 4-7 receive 0.5mg twice daily and day 8 until the end of treatment receive 1mg twice daily.<br>* Other names: Chantix;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 5: Buproprion, Intense Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive Buproprion, counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Bupropion<br>* Patients will begin with a dose of 150 mg every morning for 3 days. Then dosage will increase to 150 mg twice daily (morning and evening), for a total daily dose of 300 mg, for 7 to 12 weeks.<br>* Other names: Wellbutrin XL, Forfivo XL, Zyban, and Aplenzin;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 6: Buproprion, Intense Counselling<br>Patients diagnosed with tobacco-related treatment will receive Buproprion and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Bupropion<br>* Patients will begin with a dose of 150 mg every morning for 3 days. Then dosage will increase to 150 mg twice daily (morning and evening), for a total daily dose of 300 mg, for 7 to 12 weeks.<br>* Other names: Wellbutrin XL, Forfivo XL, Zyban, and Aplenzin;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 7: Buproprion, Minimal Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive Buproprion, counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Bupropion<br>* Patients will begin with a dose of 150 mg every morning for 3 days. Then dosage will increase to 150 mg twice daily (morning and evening), for a total daily dose of 300 mg, for 7 to 12 weeks.<br>* Other names: Wellbutrin XL, Forfivo XL, Zyban, and Aplenzin;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 8: Buproprion, Minimal Counselling<br>Patients diagnosed with tobacco-related treatment will receive Buproprion and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Bupropion<br>* Patients will begin with a dose of 150 mg every morning for 3 days. Then dosage will increase to 150 mg twice daily (morning and evening), for a total daily dose of 300 mg, for 7 to 12 weeks.<br>* Other names: Wellbutrin XL, Forfivo XL, Zyban, and Aplenzin;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 9: Nicotine, Intense Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive long acting nicotine replacement therapy (e.g. nicotine patch), counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Long-acting nicotine replacement therapy<br>* Nicotine replacement therapy (NRT) patches will be used daily from 1-10 weeks depending on participant's smoking history.<br>* Other names: Transdermal nicotine;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 10: Nicotine, Intense Counselling<br>Patients diagnosed with tobacco-related treatment will receive long acting nicotine replacement therapy (e.g. nicotine patch) and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Long-acting nicotine replacement therapy<br>* Nicotine replacement therapy (NRT) patches will be used daily from 1-10 weeks depending on participant's smoking history.<br>* Other names: Transdermal nicotine;Behavioral: High-intensity counseling<br>* A counselor will provide eight sessions in the first 8 weeks of the study. Up to three follow up sessions over the next 4 months of study will be encouraged, but not required.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 11: Nicotine, Minimal Counselling and NRT<br>Patients diagnosed with tobacco-related treatment will receive long acting nicotine replacement therapy (e.g. nicotine patch), counseling, and nicotine replacement therapy (PRN NRT). Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Long-acting nicotine replacement therapy<br>* Nicotine replacement therapy (NRT) patches will be used daily from 1-10 weeks depending on participant's smoking history.<br>* Other names: Transdermal nicotine;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Drug: Nicotine Replacement Products<br>* Participants in this group will receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|
| Experimental: Group 12: Nicotine, Minimal Counselling<br>Patients diagnosed with tobacco-related treatment will receive long acting nicotine replacement therapy (e.g. nicotine patch) and counseling. Dose and frequency will be based on patient preference, smoking history and other medical factors. | Drug: Long-acting nicotine replacement therapy<br>* Nicotine replacement therapy (NRT) patches will be used daily from 1-10 weeks depending on participant's smoking history.<br>* Other names: Transdermal nicotine;Behavioral: Low-intensity counseling<br>* A study coordinator or a member of the treatment team will provide a minimum level of initial counseling, approximately 10-20 minutes in length.<br>Other: No nicotine replacement therapy<br>* Participants in this group will not receive per required need nicotine replacement therapy.<br>* Other names: nicotine gum, nicotine losenges, nicotine spray;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants that quit smoking. | Proportion of participants that quit smoking at the 8 week assessment | at week 8 | 
| Prevalence of cigarette use | Seven day point prevalence of cigarette use will be determined from participant reports and CO testing. | at week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of cigarette use | Seven day point prevalence of cigarette use will be determined from participant reports and CO testing. | 6 months | 
| Preferred treatment | Proportion of participants preferring the treatment plan. | at baseline | 
| Change in Cigarette Use | Cigarette use will be recorded at weeks one, four, eight and at 6 months. | 6 months | 
| Drug Compliance | Subjects who complete 75% of the planned dosages of therapy will be considered compliant. | 6 months | 
| Counselling Compliance | Subjects who complete 60% of planned therapy sessions will be considered compliant. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Addiction, Cancer Therapy, Tobacco, nicotine