Esomeprazole for Esophagitis

(EERENs Trial)

Overseen By Soumyajit Roy, MD, MSc.(c)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rush University Medical Center

Must not be taking: Clopidogrel, Nelfinavir, others

Disqualifiers: Gastroesophageal cancer, Severe dysphagia, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Duration of TRT (typically 6-7 weeks)

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests esomeprazole, a common heartburn medication, to determine its effectiveness for people with esophagitis (inflammation of the esophagus) undergoing treatment for locally advanced non-small cell lung cancer (NSCLC). The researchers aim to discover if esomeprazole can reduce esophagus irritation during chemotherapy and radiation therapy. People with stage III NSCLC who are receiving both chemotherapy and radiation, and who do not have severe swallowing issues or a history of certain stomach problems, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you are currently taking clopidogrel, nelfinavir, rilpivirine, methotrexate, rifampin, digoxin, tacrolimus, or phenytoin, you will need to stop these medications as they may interact with esomeprazole.

Is there any evidence suggesting that esomeprazole is likely to be safe for humans?

Research has shown that esomeprazole is generally safe for use. Clinical trials have demonstrated its effectiveness in treating conditions like erosive esophagitis and GERD (a type of acid reflux), significantly improving symptoms.

One study compared esomeprazole to another medication and found it to be a safe choice for patients. Another report from several trials involving nearly 10,000 participants found it well-tolerated, even in older adults. These studies suggest that esomeprazole might also be safe for other uses, such as during radiation therapy for lung cancer.

Overall, evidence indicates that esomeprazole is a safe treatment option with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for esophagitis primarily involve acid suppression using proton pump inhibitors (PPIs) like omeprazole or pantoprazole. However, esomeprazole stands out because it's a more refined version of these commonly used PPIs, offering potentially better and more consistent acid control. Researchers are excited about esomeprazole's ability to complement thoracic radiation therapy and chemotherapy, potentially reducing esophagitis symptoms more effectively during cancer treatment. Additionally, its specific dosage and timing—taken before breakfast daily, even during weekends and any treatment gaps—aim to optimize its protective effects on the esophagus.

What evidence suggests that esomeprazole might be an effective treatment for esophagitis?

Research has shown that esomeprazole effectively heals erosive esophagitis (EE), a condition where the esophagus lining becomes inflamed. Studies have found that taking esomeprazole once daily heals more patients with this condition compared to other treatments. For example, after eight weeks, esomeprazole led to significant healing improvements. By controlling stomach acid, esomeprazole enhances healing results. In this trial, participants will receive esomeprazole alongside thoracic radiation therapy and concomitant chemotherapy, suggesting that esomeprazole may help with esophagitis caused by such treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Soumyajit M Roy, PhD

Principal Investigator

Rush University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage III non-small cell lung cancer (NSCLC) who are about to receive thoracic radiation and chemotherapy. They must be able to consent, follow the visit schedule, and have an ECOG score of 0-2. Women who can bear children need a negative pregnancy test. Participation in another trial may be okay if allowed.

Inclusion Criteria

Double inclusion in any ongoing trial (if the other trial permits) will be allowed

Patient or patient's legal representative is willing and able to provide written informed consent and HIPAA authorization prior to performance of any study related activity

Patient is willing and able to comply with scheduled visits and treatment schedules

Exclusion Criteria

Patient has known or suspected allergic response and prior adverse drug reaction with proton pump inhibitors

I have inflammation in my kidneys.

I have had cancer in my stomach or where my esophagus meets my stomach.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive thoracic radiation therapy with concomitant chemotherapy and esomeprazole 40 mg daily

Duration of TRT (typically 6-7 weeks)

Weekly visits for radiation therapy

Post-Treatment

Participants continue esomeprazole for 2 weeks after completion of thoracic radiation therapy

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months from the start of TRT

Visits at 2 weeks post-TRT and 3 months from start of TRT

What Are the Treatments Tested in This Trial?

Interventions

• Esomeprazole

Trial Overview The study tests whether Esomeprazole 40 mg can prevent or reduce esophagitis caused by radiation therapy in NSCLC patients receiving combined chemo (and possibly immunotherapy).

How Is the Trial Designed?

Group I: Esomeprazole 40 mg daily with thoracic radiation therapy and concomitant chemotherapy Experimental Treatment 1 Intervention

Enrolled patients will receive 40 mg of esomeprazole (two pills of 20 mg strength of esomeprazole) once daily before breakfast for the entire duration of TRT (including the weekends and any interim gap period) and for two weeks after completion of thoracic radiation therapy (TRT). TRT will be delivered as per the discretion of the treating physicians.

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Published Research Related to This Trial

In a study of 47 mechanically ventilated patients at high risk for stress ulcers, intravenous esomeprazole effectively maintained gastric acidity above pH 5 and prevented bleeding of the gastric mucosa, demonstrating its safety and efficacy as a preventive treatment.

No instances of gastric mucosal bleeding were observed, and the study suggests that esomeprazole could be a reliable option for preventing stress ulcers in ICU patients, although further comparative studies with other treatments are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency and safety of the intravenous application of esomeprazole (nexium - Astra Zeneca) in high risk patients subjected to mechanic ventilation]. Stefanov, Ch., Batashki, I., Dimitrov, D., et al.[2018]

Long-term treatment combining somatostatin analogs (SSA) and pegvisomant (PEG-V) in 86 acromegalic patients over an average of 29.2 months appears to be safe, with manageable side effects.

A significant number of patients (14) experienced tumor shrinkage of more than 20% during this combined therapy, indicating its efficacy in reducing tumor size in acromegaly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients. Neggers, SJ., de Herder, WW., Janssen, JA., et al.[2016]

Esomeprazole, a proton pump inhibitor, is more effective than omeprazole in controlling stomach acid and treating erosive esophagitis in patients with GERD.

The safety profile of esomeprazole is comparable to that of omeprazole, with infrequent adverse events, making it a reliable option for both healing erosive esophagitis and eradicating Helicobacter pylori infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esomeprazole magnesium (Nexium). Baker, DE.[2013]

In a study of 1904 patients with symptoms of gastroesophageal reflux disease (GERD), continuous daily treatment with esomeprazole 20 mg provided slightly better relief from heartburn compared to on-demand treatment.

However, the on-demand use of esomeprazole 20 mg resulted in lower direct medical costs, making it a more economical option while still being well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term treatment of patients with symptomatic gastroesophageal reflux disease comparing costs and efficacy over 6 months of treatment with Nexium On-Demand Treatment or Nexium continuous treatment. An open, randomised multi-center study]. Beglinger, C., Thalmann, C., Szucs, T., et al.[2013]

Esomeprazole sodium remains chemically and physically stable for at least 2 days at room temperature and 5 days when refrigerated, making it suitable for short-term infusion use.

The study found no significant loss of drug content (less than 7%) in esomeprazole samples across various infusion solutions, indicating its reliability for treating gastroesophageal reflux disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and chemical stability of esomeprazole sodium solutions. Kupiec, TC., Aloumanis, V., Ben, M., et al.[2022]

Esomeprazole is more effective than omeprazole and lansoprazole in healing erosive esophagitis and resolving heartburn, as shown in large trials where patients took esomeprazole 40 mg daily for 8 weeks.

It is well-tolerated and has a similar safety profile to omeprazole, with effective maintenance of healed erosive esophagitis over 6 to 12 months, and it also effectively eradicates Helicobacter pylori when used in combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of esomeprazole in the treatment of acid disorders. Johnson, DA.[2019]

In a study of 113 patients with reflux esophagitis grades C and D, esomeprazole 40 mg daily for 6 months was effective in promoting healing, regardless of the patients' CYP2C19 genotypes.

A higher body mass index (BMI) over 25 kg/m² was linked to lower healing rates, while reducing BMI by more than 1.5 kg/m² significantly improved healing outcomes, suggesting weight management could enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body mass index can determine the healing of reflux esophagitis with Los Angeles Grades C and D by esomeprazole. Sheu, BS., Chang, WL., Cheng, HC., et al.[2014]

The study identified new alpha(2)-adrenergic receptor ligands that show significant agonism at alpha(2C) receptors and antagonism at alpha(2A) receptors, which could enhance morphine's pain-relieving effects.

Compounds 8 and 11 may serve as beneficial adjuvants in pain management, potentially improving analgesia while reducing sedation associated with morphine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine? Cardinaletti, C., Mattioli, L., Ghelfi, F., et al.[2013]

Esomeprazole 40mg once daily is significantly more effective than omeprazole 20mg once daily for healing reflux oesophagitis, with healing rates of 93.4% versus 86.2% after 8 weeks, respectively.

The treatment with esomeprazole also results in cost savings of £1290 (14%) over 8 weeks compared to omeprazole, making it a more cost-effective option for the acute treatment of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK. Wahlqvist, P., Junghard, O., Higgins, A., et al.[2018]

In a study of 188 patients with acromegaly, factors such as IGF-I levels, weight, height, and age were found to significantly predict the optimal dose of pegvisomant (PEGV) needed to normalize IGF-I levels when used alongside long-acting somatostatin analogues (LA-SSAs).

For patients receiving PEGV as monotherapy, only weight was a significant predictor of the required dose, indicating that dosing strategies may need to be tailored based on individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues. Franck, SE., Korevaar, TIM., Petrossians, P., et al.[2019]

Pegvisomant was found to be significantly more effective than octreotide in suppressing the growth hormone (GH) axis, achieving up to 62% suppression of total IGF-I levels after 14 days of treatment in 80 healthy subjects.

The safety profile of pegvisomant was favorable, with most adverse events being mild (grade 1 or 2), including injection site reactions, headache, and fatigue, suggesting it could be a viable option for treating GH-dependent tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacodynamic effects of the growth hormone receptor antagonist pegvisomant: implications for cancer therapy. Yin, D., Vreeland, F., Schaaf, LJ., et al.[2016]

Esomeprazole (40 mg) is more effective than omeprazole (20 mg) in healing reflux oesophagitis, with higher healing rates observed at both 4 weeks (relative risk 1.14) and 8 weeks (relative risk 1.08) based on a systematic review of randomized controlled trials.

Other proton pump inhibitors like lansoprazole, pantoprazole, and rabeprazole did not show superior healing rates compared to omeprazole, indicating that esomeprazole may be a preferred option for treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis. Edwards, SJ., Lind, T., Lundell, L.[2019]

Esomeprazole (Nexium) is more effective than other proton pump inhibitors in controlling stomach acid, maintaining a higher intragastric pH for longer periods in patients with gastroesophageal reflux disease after just 5 days of treatment.

In clinical trials, esomeprazole 40 mg once daily for up to 8 weeks resulted in higher healing rates of erosive esophagitis and better heartburn resolution compared to omeprazole and lansoprazole, making it a strong option for treating acid-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of esomeprazole in patients with acid-peptic disorders. Beck, J.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11172701/

RETRACTED: A Phase III Head-to-Head Study to Compare ... At 4 weeks, the EE healing rate was 90.3% (93/103) in the fexuprazan 40 mg group and 88.5% (92/104) in the esomeprazole 40 mg group. At 8 weeks, it was 99.1% ( ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000292700002236X

Esomeprazole once daily for 6 months is effective therapy ... Esomeprazole 40 mg and 20 mg once daily for 8 wk healed a significantly greater proportion of patients with erosive esophagitis than did omeprazole 20 mg once ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2700419/

Comparison of esomeprazole enteric-coated capsules vs ... The ulcer healing rates at the end of wk 2 were 86.7% and 85.2% in the esomeprazole enteric-coated capsules and esomeprazole magnesium groups, respectively (P = ...

4. eurekalert.org eurekalert.org/news-releases/822627

New study shows erosive esophagitis healing linked to ... Patients were more likely to achieve healing of erosive esophagitis (EE) if their gastric acid was well controlled after five days of therapy.

5. cghjournal.org cghjournal.org/article/S1542-3565(06)00941-4/fulltext

Esomeprazole Versus Other Proton Pump Inhibitors in ... Esomeprazole confers a statistically significant improvement, yet, clinically, only a modest overall benefit in 8-week healing and symptom relief in all-comers ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9730436/

Randomized controlled trial to evaluate the efficacy and safety ... This study results indicate that fexuprazan 40 mg once daily can be an alternative of esomeprazole 40 mg once daily for patients with erosive esophagitis in ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/022101s014021957s017021153s050lbl.pdf

NEXIUM (esomeprazole magnesium) Label In general, NEXIUM was well tolerated in both short and long-term clinical trials. The safety in the treatment of healing of erosive esophagitis was assessed in ...

8. ema.europa.eu ema.europa.eu/en/documents/assessment-report/nexium-control-epar-public-assessment-report_en.pdf

nexium-control-epar-public-assessment-report_en.pdf - EMA The safety events for elderly patients from pooled data from 24 placebo-controlled clinical studies with esomeprazole comprising 9877 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8215048/

Efficacy and Safety of Esomeprazole for the Treatment of ... Esomeprazole treatment yielded a significant improvement in clinical signs and symptoms of GERD compared to placebo group.

10. sciencedirect.com sciencedirect.com/science/article/pii/S1551714423002422

High dose esomeprazole as an anti-inflammatory agent in ... These findings suggest that high-dose esomeprazole has immunomodulatory effects and might improve clinically relevant outcomes in patients with sepsis.