A Phase 3 interventional study of esomeprazole and Placebo in Nausea, sponsored by Baylor Breast Care Center. Terminated at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-12-06.
Sponsored by Baylor Breast Care Center · Phase 3, Interventional, and Treatment
This study will look at a drug called esomeprazole, the newest PPI, as a way to further reduce the amount of nausea and vomiting seen in breast cancer patients receiving adriamycin or epirubicin chemotherapy. Esomeprazole may help protect the gut lining from the stomach acid and thus lessen the nausea and vomiting. If patients have less stomach sickness, they may be able to enjoy their daily routines much more while they are getting chemotherapy.
Breast Cancer
The American Cancer Society estimates that there will be approximately 215,990 new cases of breast cancer diagnosed in women during 2004 in the United States. Breast cancer is the most common malignancy in women in the United States and the second leading cause of cancer death in women.
Treatment options for breast cancer have evolved from extensive surgical approaches to breast-conserving techniques and the use of adjuvant and neo-adjuvant chemotherapy, radiation, and endocrine therapy to reduce the risk of recurrence.
Chemotherapy in Breast Cancer
The use of adjuvant chemotherapy is a well established and routine part of care for breast cancer. Chemotherapy can reduce a woman's risk of recurrence by 25-30%. The amount of risk reduction depends on the patient's age, nodal status, and hormone receptor status.
Anthracycline-based chemotherapy is standard in the treatment of breast cancer with doxorubicin being the most frequently used agent in this group. Currently the most commonly used chemotherapy regimens for breast cancer include: * doxorubicin/cyclophosphamide (AC) * fluorouracil/doxorubicin/cyclophosphamide (FAC) * cyclophosphamide/methotrexate/fluorouracil (CMF) * docetaxel/doxorubicin/cyclophosphamide (TAC) * fluorouracil/epirubicin/cyclophosphamide (FEC) * single agent taxanes (paclitaxel and docetaxel) Except for the taxanes, these agents are known to cause significant nausea and vomiting after administration.
Cancer drugs differ both quantitatively and qualitatively in their emetogenic potential. Emetogenic potential can be influenced by chemotherapy-related characteristics and patient characteristics.
Nausea and vomiting following administration of chemotherapy for cancer are among the most significant and feared side effects of patients undergoing treatment. Despite continued advances in pharmacology, the ability to prevent or control nausea, vomiting, or retching remains a problem for patients. Research has confirmed that chemotherapy related nausea and vomiting negatively affects quality of life. Among patients, the same level of nausea and vomiting varies in effect on quality of life. It is difficult to substantiate the degree of this effect, but it has been shown that even with serotonin antagonists, patients still rank nausea as their most bothersome chemotherapy side effect, while vomiting is ranked as third to fifth most bothersome.
The risk for chemotherapy induced nausea and vomiting is related to the anti-neoplastic agents administered and to patient related factors. Emetogenic potential is affected by the intrinsic emetogenicity of the chemotherapy drugs, the combination of agents, the doses administered and the rate of administration. Patient related factors include: 1. gender-increased risk in females 2. age-increased risk in younger, premenopausal patients 3. history of alcohol intake-low chronic intake decreases risk 4. history of motion sickness-increases risk 5. hyperemesis during pregnancy-increases risk.
Emesis is a complex phenomenon characterized by three components: nausea, vomiting, and retching. Nausea is a subjective phenomenon of an unpleasant sensation in the epigastrium and in the back of the throat that may or may not culminate in vomiting; it is also described as feeling "sick at the stomach." Nausea exists only insofar as it is defined by the patient. Vomiting is the forceful expulsion of the contents of the stomach, duodenum and jejunum through the oral cavity as a result of changes in intrathoracic positive pressure. It is also described as "throwing up." Retching, also called "dry heaves," is the attempt to vomit without expelling any material.
Drugs used to improve the control of nausea and vomiting include serotonin antagonists, dopamine antagonist (metoclopramide, prochlorperazine), corticosteroids, benzodiazepines, and phenothiazines. The American Society of Clinical Oncology (ASCO) has developed clinical practice guidelines for the management of chemotherapy-induced nausea and vomiting based on the emetogenic potential of the agents being administered. For combinations with moderate emetogenic potential, acute emesis is managed with a corticosteroid and serotonin receptor antagonists. Serotonin receptor antagonists currently available include ondansetron, granisetron, and dolasetron. Studies indicate they are equally effective in the management of chemotherapy-related nausea/vomiting/retching. Delayed emesis (greater than 24 hours post-chemotherapy) can be controlled with a number of agents including steroids, serotonin receptor antagonists or metoclopramide. Recommended combinations include dexamethasone, 8 mg for 2-3 days, then 4 mg for 1-2 days and metoclopramide, 20-40 mg twice daily to four times daily for 3-4 days, or Zofran 8 mg twice daily for 3 days. With combination chemotherapy, patients should receive the antiemetic regimens appropriate for the chemotherapy agent with the highest emetic risk.
Drugs used to improve the control of nausea and vomiting include serotonin antagonists, dopamine antagonist (metoclopramide, prochlorperazine), corticosteroids, benzodiazepines, and phenothiazines. The American Society of Clinical Oncology (ASCO) has developed clinical practice guidelines for the management of chemotherapy-induced nausea and vomiting based on the emetogenic potential of the agents being administered. For combinations with moderate emetogenic potential, acute emesis is managed with a corticosteroid and serotonin receptor antagonists. Serotonin receptor antagonists currently available include ondansetron, granisetron, and dolasetron. Studies indicate they are equally effective in the management of chemotherapy-related nausea/vomiting/retching. Delayed emesis (greater than 24 hours post-chemotherapy) can be controlled with a number of agents including steroids, serotonin receptor antagonists or metoclopramide. Recommended combinations include dexamethasone, 8 mg for 2-3 days, then 4 mg for 1-2 days and metoclopramide, 20-40 mg twice daily to four times daily for 3-4 days, or Zofran 8 mg twice daily for 3 days. With combination chemotherapy, patients should receive the antiemetic regimens appropriate for the chemotherapy agent with the highest emetic risk.
Studies done with standard antiemetics in women undergoing treatment with anthracycline-based chemotherapy for breast cancer show a success rate for emetic control in the range of 60-65%. 4. Measurement of Nausea, Vomiting, and Retching
It remains difficult to compare clinical studies of nausea and vomiting because of the variety of measurement tools utilized and the variable time periods that were monitored following chemotherapy. The ideal tool would include assessment of: 1. duration and severity of nausea 2. frequency, duration, and severity of vomiting/retching 3. number of antiemetics utilized 4. impact of nausea and vomiting on quality of life 5. adverse effects experienced
Despite utilization of the antiemetics recommended by ASCO, approximately one-third of patients undergoing anthracycline-based chemotherapy still develop nausea and vomiting. A current therapeutic challenge is to find and prove methods to control nausea and vomiting after chemotherapy.
Although the pathophysiology of nausea and vomiting is not well understood, we know that chemotherapy causes damage to the gastrointestinal (GI) mucosa. The pathobiology of the mucosal damage has been reviewed by Blijlevens and can be divided into four phases: the inflammatory phase, the epithelial phase, the ulcerative/bacteriological phase and the healing phase. This mucosal injury is usually self-limiting with a complete cycle of injury to healing lasting approximately 2-3 weeks. The mucosal damage can be increased in patients receiving chemotherapy and corticosteroids which breast cancer patients require as pre-medications. Since cytotoxic chemotherapy damages the mucosal lining, it leaves the GI mucosa exposed to the normal acid-producing gastric parietal cells. The resultant damage has been seen endoscopically in patients receiving chemotherapy with cytosine arabinoside. Hence, suppression of acid secretion from the gastric parietal cells should reduce mucosal injury and related symptoms.
Historical therapies for gastrointestinal distress have included anticholinergics, as well as H-2 receptor antagonists, to help reduce acid secretion. H-2 receptor blockers were effective by blocking the histamine driven acid secretion, but despite its targeted action, acid production continues through alternative pathways. Recently a group of new agents known as proton pump inhibitors have been developed which target the final common pathway of acid secretion. These agents are known to act directly on the H+/K+-ATPase in the gastric parietal cell. Since these agents act directly on the final stimulatory pathway, they provide rapid symptom resolution and reliable healing in gastroesophageal reflux disease and peptic ulcer disease.
To date, two large clinical trials have been performed to evaluate the effectiveness of proton pump inhibitors in preventing mucosal injury. The first trial selected 182 patients with breast cancer (77 pts) or colon cancer (105 pts) who were receiving cyclophosphamide, methotrexate and 5-FU (CMF), or 5-FU, respectively. These patients were randomized to receive either omeprazole (20 mg daily), misoprostol (a prostaglandin analogue) (400 mg twice daily), or placebo (once daily) for two full courses of chemotherapy (56 days). Endoscopic evaluation (EGD) was performed one week prior to initiation of chemotherapy and one week after the end of the second cycle of chemotherapy comparing the number of erosions/ulcers in the stomach and duodenum. The omeprazole group had a lower frequency and degree of erosions compared to placebo and misoprostol. Symptoms of epigastric pain and heartburn were also significantly less in the omeprazole patients. A second study performed by the same group evaluated patients with breast or colon cancer (n=228) receiving either CMF or 5-FU. These patients were randomized to receive omeprazole 20 mg daily, ranitidine 300 mg daily (a H2 blocker), or placebo once daily for 56 days. EGD was performed as above, before cycle 1 and after cycle 2 of chemotherapy. The omeprazole group experienced the lowest frequency of ulcers (n=2), followed by the ranitidine group (n=8), and the placebo group (n=18). Symptoms of epigastric pain or heartburn were also significantly less in the omeprazole arm (n=11) compared to the ranitidine (n=13) or placebo (n=24) arms. Chemotherapy was delayed in the placebo and ranitidine group, but not in the patients receiving omeprazole. These two trials demonstrate the ability of a proton pump inhibitor (omeprazole) to limit the mucosal injury induced by chemotherapy. Protecting the mucosa from damage also appeared to significantly decrease the frequency of upper GI symptoms. It should be noted that nausea or vomiting was not assessed in either trial since various antiemetics were given during chemotherapy.
Esomeprazole magnesium is the latest proton pump inhibitor that has been developed. It is unique in that it is the S- isomer of omeprazole, and as such, has better bioavailability and elevated levels compared to the racemic omeprazole. Since the proton pump is the last step in acid production, blockade of this pump causes reduction in gastric acidity. This effect is dose related up to a dose of 20-40mg daily. Esomeprazole is currently clinically indicated for the treatment of erosive esophagitis and symptomatic gastroesophageal reflux disease. In addition, it is approved to treat Helicobacter pylori in patients with duodenal ulcer disease in conjunction with either amoxicillin or clarithromycin and amoxicillin.
644 studies on the registry are indexed under Nausea; 85 are open to participants now.
This study's enrollment of 43 is below the median of 96 across 544 interventional studies indexed under Nausea.
Browse Nausea studies →Baylor Breast Care Center is the lead sponsor of 16 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For inclusion, participants must:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receiving chemotherapy (anthracycline-based) will be randomized to esomeprazole for Cycle 1 Days 1-5 and Cycle 2 Days 1-5
Drug: esomeprazole
Subjects will be given placebo Cycle 1 Days 1-5 and Cycle 2 Days 1-5.
Other: Placebo
nexium
Also known as: nexium
Placebo 1 pill daily Cycle 1 Days 1-5 and Cycle 2 Days 1-5
Also known as: Sugar Pill
Number of Times a Subject Felt Sick to Her Stomach and Number of Times a Subject Required Rescue Medication
Proportion of patients who exhibit no more than one emetic episode and who do not require rescue medication for nausea from 2-7 days following chemotherapy. Thus, we will look at esomeprazole when used to decrease the incidence,severity and duration of nausea/vomiting/retching in breast cancer patients who are receiving anthracycline-based chemotherapy.
Time frame: 2-7 days following chemotheraphy
| Milestone | Esomeprazole | Sugar Pill |
|---|---|---|
| Started | 21 | 22 |
| Completed | 16 | 18 |
| Not completed | 5 | 4 |
| Withdrew: Protocol violation | 1 | 2 |
| Withdrew: Adverse event | 4 | 2 |
Proportion of patients who exhibit no more than one emetic episode and who do not require rescue medication for nausea from 2-7 days following chemotherapy. Thus, we will look at esomeprazole when used to decrease the incidence,severity and duration of nausea/vomiting/retching in breast cancer patients who are receiving anthracycline-based chemotherapy.
| Proportion of patients who exhibit no mo | Esomeprazole | Sugar Pill |
|---|---|---|
| cycle 1 | 0.8 | 0.8 |
| cycle 2 | 0.94 | 1 |
Collected over Adverse events were collected after the subjects was enrolled to the study, during the study treatment, and followed up 30 days after termination from the study.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Esomeprazole | — | 0/21 (0%) | 15/21 (71.4%) |
| Sugar Pill | — | 0/22 (0%) | 16/22 (72.7%) |
| Event | Esomeprazole | Sugar Pill |
|---|---|---|
| headacheGeneral disorders | 7/21 | 8/22 |
| nauseaGastrointestinal disorders | 4/21 | 7/22 |
| fatigueGeneral disorders | 4/21 | 3/22 |
| mild nauseaGastrointestinal disorders | 4/21 | 3/22 |
| severe nauseaGastrointestinal disorders | 4/21 | 2/22 |
| diarrheaGastrointestinal disorders | 1/21 | 4/22 |
| belchingGastrointestinal disorders | 3/21 | 0/22 |
| vomitingGastrointestinal disorders | 3/21 | 2/22 |
| constipationGastrointestinal disorders | 1/21 | 3/22 |
| bone painMusculoskeletal and connective tissue disorders | 2/21 | 0/22 |
| Age, Customized(participants) | Esomeprazole | Sugar Pill | Total |
|---|---|---|---|
| <40 years | 2 | 3 | 5 |
| Between 40 and 49 years | 4 | 6 | 10 |
| Between 50 and 59 years | 11 | 8 | 19 |
| Between 60 and 69 years | 4 | 3 | 7 |
| >=70 years | 0 | 2 | 2 |
| Sex: Female, Male(Participants) | Esomeprazole | Sugar Pill | Total |
|---|---|---|---|
| Female | 21 | 22 | 43 |
| Male | 0 | 0 | 0 |
The record gives a start of Aug 2005, a primary completion of Feb 2009 and a completion of Feb 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Mar 2012, 3 years 1 month after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Nov 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Esomeprazole
Baylor Breast Care Center