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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best ways to help people with tobacco-related cancer quit smoking. It tests various combinations of medications, such as bupropion (an antidepressant used for smoking cessation), varenicline (a medication that reduces cravings and withdrawal symptoms), and nicotine patches, along with counseling support. The researchers aim to determine if allowing patients to choose their quitting method improves their chances of success. This trial suits those diagnosed with tobacco-related cancer, who have smoked recently, and have a long history of smoking. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial have been studied for safety. Here's a breakdown:

1. **Bupropion**: Studies have shown that bupropion is generally safe for helping people quit smoking and is FDA-approved for this purpose. However, excessive doses can increase the risk of seizures. Keeping the dose at 300 mg per day helps manage this risk.

2. **Varenicline**: Research has found varenicline effective in helping people quit smoking. The most common side effects include nausea and headaches. Some individuals may also experience mood changes or sleep disturbances.

3. **Nicotine Replacement Therapy (NRT)**: NRT, such as nicotine patches or gum, is widely used and proven safe. It can cause minor side effects like skin irritation from the patch or a sore throat from the gum, but these are usually not serious.

Overall, these treatments are well-tolerated, and many people use them to quit smoking. Always consult a healthcare provider to determine the best option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for smoking cessation in cancer patients because they explore varied combinations of medications and counseling intensities to tackle tobacco addiction effectively. Unlike standard nicotine replacement therapies that typically involve just patches or gums, these treatments combine long-acting nicotine replacements, like patches, with medications such as Varenicline and Bupropion, which target brain chemistry to reduce cravings. Additionally, the trial examines how different levels of counseling support can optimize quitting success, offering a personalized approach based on patient preferences and smoking history. This comprehensive strategy could enhance quit rates among cancer patients, who often face unique challenges when trying to stop smoking.

What evidence suggests that this trial's treatments could be effective for smoking cessation in cancer patients?

Studies have shown that certain treatments can help people quit smoking. In this trial, participants may receive Varenicline, which has proven particularly effective, with about 45.5% of people successfully quitting. Another group will receive Bupropion combined with nicotine replacement therapy (NRT), which increases the chances of quitting by 20% compared to other methods. Participants in other groups may receive NRT alone, which can improve quitting success by 50%. These treatments reduce cravings and withdrawal symptoms, making it easier to stop smoking. ^{1 6 7 8 9}

Who Is on the Research Team?

Joseph Valentino, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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 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 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]

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]

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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10858725/

A Review of Smoking Cessation Interventions - PubMed Central Moreover, attempting to quit smoking without any structured approach yielded a mere 3%-5% success rate within the same timeframe [7]. This study ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/217331

Bupropion for Smoking Cessation: A Randomized Trial One of these clinical studies reported an absolute 20% increase in 1-year quit rates among participants receiving combined bupropion plus NRT compared with ...

3. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000031.pub5/full

Antidepressants for smoking cessation - Howes, S - 2020 Using the antidepressant, bupropion, makes it 52% to 77% more likely that a person will successfully stop smoking, which is equal to five to ...

4. tobaccoinduceddiseases.org tobaccoinduceddiseases.org/Comparative-assessment-of-outcomes-of-smoking-cessation-ntherapies-and-role-of-free,136422,0,2.html

Comparative assessment of outcomes of smoking ... The overall quit rate was 31.8% by the primary intervention (varenicline: 45.5%, bupropion: 38.2%, NRT: 33%, psychosocial support: 4.2%), and quit rate was ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2528204/

The use of bupropion SR in cigarette smoking cessation In patients with established CVD, bupropion has similar success rates compared with healthy smokers (27% bupropion vs 11% placebo at 26 weeks, 22% vs 9% at 52 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/020711s052lbl.pdf

Zyban - accessdata.fda.gov The risk of seizure can be reduced if the dose of ZYBAN for smoking cessation does not exceed. 300 mg per day, given as 150 mg twice daily, and titration ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470212/

Bupropion - StatPearls - NCBI Bookshelf - NIH Bupropion is generally avoided due to limited safety data. ... Tolerability and safety of sustained-release bupropion in the management of smoking cessation.

8. cdc.gov cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-bupropion-sr.html

How to Use Bupropion SR | Quit Smoking There are seven medicines approved by the Food and Drug Administration (FDA) to help you quit. They work in different ways. All have been shown to be safe ...

9. aafp.org aafp.org/pubs/afp/issues/2024/0500/cochrane-antidepressants-smoking-cessation.html

Antidepressants to Aid in Smoking Cessation High-certainty evidence found that 19% of participants taking bupropion were not smoking at 6 months of therapy compared with 12% of participants receiving ...