Smoking Cessation Strategies for Cancer

(TTOP Trial)

Recruiting at 2 trial locations

Overseen By Joseph Valentino, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph Valentino, MD

Must not be taking: Varenicline, Buproprion

Disqualifiers: Psychiatric illness, Epilepsy, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

126 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently taking varenicline or buproprion, you must not have taken them within one month of enrollment.

What data supports the effectiveness of the drugs used in the Smoking Cessation Strategies for Cancer trial?

Research shows that varenicline, bupropion, and nicotine replacement therapy (NRT) are effective for smoking cessation, with varenicline being slightly more effective than bupropion and NRT. These drugs approximately double the chances of quitting smoking for a year when used for three months. ^{1 2 3 4 5}

Is the smoking cessation treatment safe for humans?

Varenicline, bupropion, and nicotine replacement therapies are generally considered safe for smoking cessation, but there have been concerns about psychiatric disturbances with varenicline and bupropion. These treatments have not been associated with increased risks during pregnancy. ^{6 7 8 9 10}

What makes the drug varenicline unique for smoking cessation in cancer patients?

Varenicline is unique because it is a selective nicotinic receptor partial agonist, specifically developed for smoking cessation, and has shown higher efficacy rates compared to bupropion and nicotine replacement therapies. It is particularly effective for cancer patients who continue to smoke, offering a novel approach compared to traditional nicotine-based treatments. ^{2 3 8 11 12}

Research Team

Joseph Valentino, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for individuals who have smoked within a month of their cancer diagnosis, have a significant history of smoking (10-pack year), and expect to live more than a year. They must be newly diagnosed or have recurrent tobacco-related cancer but can't join if they're allergic to certain quit-smoking meds, pregnant, recently had serious heart issues, uncontrolled seizures or hypertension, or are currently in another cessation program.

Inclusion Criteria

My cancer is new or has returned and is linked to tobacco use.

I have smoked the equivalent of 10 packs of cigarettes a year.

You are expected to live for at least one more year.

Exclusion Criteria

You have tried to harm yourself in the past by attempting suicide.

I have unstable chest pain.

I have not taken varenicline or buproprion in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized smoking cessation regimen including pharmaceutical therapy, counseling, and nicotine replacement therapy based on their preferences

8 weeks

Weekly visits for counseling and monitoring

Follow-up

Participants are monitored for smoking cessation success and compliance with the treatment plan

6 months

Visits at weeks 1, 4, 8, and 6 months

Treatment Details

Interventions

• Bupropion
• High-intensity counseling
• Long-acting nicotine replacement therapy
• Low-intensity counseling
• Nicotine Replacement Products
• Varenicline

Trial Overview The study aims to find the best way to help patients with tobacco-related cancers quit smoking by letting them choose their treatment from options like medications (Bupropion and Varenicline), nicotine replacement products, and counseling. Success rates will be compared with previous studies where treatments were assigned randomly rather than chosen.

Participant Groups

Group I: Group : Varenicline, Intense Counselling Experimental Treatment 3 Interventions

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.

Group II: Group 9: Nicotine, Intense Counselling and NRT Experimental Treatment 3 Interventions

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.

Group III: Group 8: Buproprion, Minimal Counselling Experimental Treatment 3 Interventions

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.

Group IV: Group 7: Buproprion, Minimal Counselling and NRT Experimental Treatment 3 Interventions

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.

Group V: Group 6: Buproprion, Intense Counselling Experimental Treatment 3 Interventions

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.

Group VI: Group 5: Buproprion, Intense Counselling and NRT Experimental Treatment 3 Interventions

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.

Group VII: Group 4: Varenicline, Minimal Counselling Experimental Treatment 3 Interventions

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.

Group VIII: Group 3: Varenicline, Minimal Counselling and NRT Experimental Treatment 3 Interventions

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.

Group IX: Group 1: Varenicline, Intense Counselling and NRT Experimental Treatment 3 Interventions

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.

Group X: Group 12: Nicotine, Minimal Counselling Experimental Treatment 3 Interventions

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.

Group XI: Group 11: Nicotine, Minimal Counselling and NRT Experimental Treatment 3 Interventions

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.

Group XII: Group 10: Nicotine, Intense Counselling Experimental Treatment 3 Interventions

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.

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

Joseph Valentino, MD

Lead Sponsor

Trials

1

Recruited

130+

Findings from Research

In a 52-week study involving 746 participants, varenicline was found to be significantly more effective than transdermal nicotine replacement therapy (NRT) for smoking cessation, with a continuous abstinence rate of 55.9% compared to 43.2% for NRT during the last 4 weeks of treatment.

Varenicline also led to significantly lower levels of craving, withdrawal symptoms, and smoking satisfaction compared to NRT, although it had a higher incidence of nausea as a side effect (37.2% for varenicline vs. 9.7% for NRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Aubin, HJ., Bobak, A., Britton, JR., et al.[2022]

Varenicline is the most effective first-line pharmacotherapy for smoking cessation, showing a significant effect compared to placebo with an odds ratio of 2.27, followed by bupropion (1.69) and nicotine replacement therapy (1.60).

Despite some safety concerns, regulatory agencies deem bupropion and varenicline to have a favorable benefit/risk profile, but healthcare providers should monitor patients for potential neuropsychiatric symptoms, especially in those with psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Aubin, HJ., Luquiens, A., Berlin, I.[2022]

In a study of 11,968 participants in Taiwan, varenicline was found to be more effective than nicotine replacement therapy (NRT) patch in achieving smoking abstinence, with higher odds ratios for 7-day, 1-month, and 6-month point-prevalence rates.

Varenicline showed significant benefits for both women and smokers with light to moderate nicotine dependence, indicating its effectiveness across different demographics and levels of nicotine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. Chang, PY., Lo, PC., Chang, HC., et al.[2018]

Nicotine replacement therapy (NRT) is recommended as the first-line treatment for smoking cessation due to its well-documented efficacy and mild side effects, with a 1-year quit rate of about 20-25% when combined with counseling.

Varenicline is slightly more effective than bupropion SR for quitting smoking, but both are suitable options for individuals who have not succeeded with NRT, especially considering the potential side effects associated with bupropion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? Tønnesen, P.[2017]

In a study of 227 patients at a smoking cessation clinic, the combination of bupropion and a nicotine patch showed a higher 2-month abstinence rate (37%) compared to bupropion alone (26%), although this difference was not statistically significant (p = 0.1).

At 6 months, the abstinence rates were 42% for the bupropion group and 35% for the combination therapy group, indicating that while combination therapy may offer short-term benefits, there was no significant difference in long-term abstinence rates (p = 0.4) and both treatments were generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the tolerability and effectiveness of two treatment regimens in a smoking clinic. Sherman, SE., Aldana, I., Estrada, M., et al.[2019]

Varenicline combined with standard nicotine replacement therapy was found to be the most effective treatment for achieving sustained smoking abstinence, with an odds ratio of 5.75, while e-cigarettes also showed promise with an odds ratio of 3.22, although with high uncertainty.

Bupropion was associated with an increased risk of serious adverse events compared to placebo, and varenicline showed a higher risk of major adverse neuropsychiatric events compared to bupropion, highlighting the need for careful consideration of safety when choosing smoking cessation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation medicines and e-cigarettes: a systematic review, network meta-analysis and cost-effectiveness analysis. Thomas, KH., Dalili, MN., López-López, JA., et al.[2022]

In a study involving 294 participants, varenicline was found to be significantly more effective than placebo for smoking cessation, with lasting effects observed up to 6 months after treatment.

Varenicline not only helped with quitting smoking but also reduced symptoms of depression and negative emotions, without increasing the risk of neuropsychiatric adverse events, making it a safe option for those looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. Cinciripini, PM., Robinson, JD., Karam-Hage, M., et al.[2022]

Varenicline (Champix) is a newly approved medication for smoking cessation that acts as a partial agonist of nicotinic receptors, offering a different mechanism of action compared to traditional therapies like nicotine replacement and bupropion.

Recent studies indicate that varenicline is effective in helping individuals quit smoking and may have advantages over existing treatments, although potential side effects are also discussed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. Vandemergel, X.[2015]

Varenicline users did not show worse mental health compared to current smokers or those who quit without medication, suggesting it may be a safe option for smoking cessation in terms of psychiatric effects.

In contrast, bupropion was linked to significantly lower mental health status across all groups, indicating potential risks for users, even after accounting for pre-existing psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mental health status of varenicline and bupropion users during a quit attempt compared to current smokers, other quitters, and non-smokers. Shewale, AR., Borse, MS., Brown, JD., et al.[2022]

In a study of over 1 million deliveries in Australia, varenicline exposure during pregnancy was associated with a lower risk of adverse perinatal events compared to unexposed women, suggesting it may be a safer option than previously thought.

Varenicline-exposed infants had lower rates of prematurity, being small for gestational age, and severe neonatal complications compared to those exposed to nicotine replacement therapy (NRT), challenging the current preference for NRT over varenicline in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. Tran, DT., Preen, DB., Einarsdottir, K., et al.[2020]

Varenicline is the most effective smoking cessation treatment among nicotine replacement therapies and bupropion, with an odds ratio of 3.09 compared to placebo, indicating its strong efficacy in helping people quit smoking.

Bupropion offers unique benefits for cancer patients, such as increased energy and a lower risk of nausea and weight gain, making it a suitable option for those trying to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for tobacco cessation: nicotine agonists, antagonists, and partial agonists. Karam-Hage, M., Cinciripini, PM.[2021]

In a phase 2 study involving 411 healthy smokers, varenicline tartrate at doses of 1.0 mg once and twice daily significantly increased quit rates compared to placebo, with 48.0% and 37.3% quitting respectively, versus only 17.1% for placebo.

Varenicline was well tolerated, with discontinuation rates due to adverse events similar to placebo, indicating it is a safe and effective option for smoking cessation, especially at the 1.0 mg twice daily dose for long-term success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Nides, M., Oncken, C., Gonzales, D., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. [2018]

4. Poland pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? [2017]

5. England pubmed.ncbi.nlm.nih.gov

Comparing the tolerability and effectiveness of two treatment regimens in a smoking clinic. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Smoking cessation medicines and e-cigarettes: a systematic review, network meta-analysis and cost-effectiveness analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. [2022]

8. Belgium pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. [2015]

9. Ireland pubmed.ncbi.nlm.nih.gov

Mental health status of varenicline and bupropion users during a quit attempt compared to current smokers, other quitters, and non-smokers. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for tobacco cessation: nicotine agonists, antagonists, and partial agonists. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. [2022]