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Pantoprazole Prophylaxis Against Delayed CINV for Patients Receiving Breast Cancer Chemotherapy

Phase 2
Completed
Conditions
Oncology
Chemotherapy-induced Nausea and Vomiting
Breast Cancer
Interventions
Registration Number
NCT03948477
Lead Sponsor
University of Auckland, New Zealand
Brief Summary

This study explores whether a commonly used medication called Pantoprazole can help prevent delayed nausea and vomiting from chemotherapy for early breast cancer.

Delayed nausea, and occasionally vomiting, can occur after breast cancer chemotherapy, affecting quality of life. A potential cause of these delayed side effects is that the chemotherapy may cause stomach irritation. Pantoprazole is commonly used to treat stomach irritation by reducing stomach acid, which may in turn improve nausea and/or vomiting.

Patients undergoing breast cancer chemotherapy before or after primary surgery will be invited to participate in the study. They will be asked how much nausea or vomiting they have with and without Pantoprazole from Day 2 until 5 after they receive chemotherapy. All participants will still receive all of the usual anti-sickness medications, which are very effective in preventing sickness in the first 24 hours after treatment, but not for delayed symptoms.

Information from the study may lead to a change in practice with patients using Pantoprazole to reduce the risks of delayed nausea and vomiting.

Detailed Description

Breast Cancer is the most common cancer type in women in New Zealand and has the second highest mortality (Ministry of Health NZ) Many women with early breast cancer still receive chemotherapy, before or after surgery and delayed nausea is a particular challenge. Ensuring tolerable therapy is critical to improving outcomes, by enabling patients to complete optimal anti-cancer therapy and to improve quality of life during therapy. Despite recent advances in antiemetic regimens, recent trials showed that rates of delayed Chemotherapy-Induced Nausea and Vomiting (CINV) are is in excess of 50%, with significant impacts on quality of life during treatment. This suggests that different mechanisms than those targeted by centrally acting anti-emetics account for such symptoms. There is strong evidence that chemotherapy regimens can result in gastrointestinal mucosal injury and dyspepsia. A number of studies have shown chemotherapy-induced dyspepsia can be relieved by a proton pump inhibitor, but none have reported their use as prophylaxis for delayed CINV, which may be a linked symptom. Proton pump inhibitors are widely used in the treatment of non-malignant dyspeptic conditions and are the most potent medications at reducing gastric acid secretions. They are considered safe in short-term use and are commonly used in clinical practice in cancer patients as well as the wider population. The pharmacokinetics Pantoprazole make it the ideal PPI for this study. The experience of New Zealand Medical Oncologists is that delayed nausea is often completely resolved by the delayed use of a PPI when symptoms occur. In this study we hope to see a 30% difference in the rates of delayed nausea by using a drug which is readily available and of very low cost. This will be the first time it has been used as preventive therapy in this setting. If this benefit occurs, it would significantly improve the treatment journey and may improve compliance to anti-cancer therapies.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
160
Inclusion Criteria
  1. Men or women who are being considered for adjuvant or neoadjuvant chemotherapy with either FEC or AC or TC chemotherapy and have been deemed by their treating Oncologist as being fit for treatment. The scheduled length of each chemotherapy cycle must be 14-21 days.

  2. Age ≥18 years.

  3. Willing to comply with all study requirements, including treatment (being able to swallow tablets), timing and nature of required assessments.

  4. All patients must be able to speak and read in English to ensure consent is informed and documentation of patient-reported outcome measures can be adhered to.

  5. Signed, written informed consent.

Exclusion Criteria
  1. Patients who are receiving therapy to reduce gastric acid (including proton pump Inhibitors (e.g. Omeprazole, Pantoprazole, Lansoprazole, Esomeprazole or Histamine type-2 receptor antagonists e.g. Ranitidine)) at the time of enrolment will be excluded from the trial.

  2. Patients with pre-existing hypomagnesemia as defined by the reference range at the investigating sites laboratory.

  3. Patients with a history of cardiac arrhythmias including atrial fibrillation or paroxysmal tachycardias.

  4. Patients with known metastatic disease.

  5. The presence of any serious medical or psychiatric conditions, which might limit the ability of the patient to comply with follow up.

  6. The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow up schedule, including alcohol dependence or drug abuse.

  7. Pregnancy, lactation or inadequate contraception. Women must be postmenopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Pantoprazole/PlaceboPantoprazole 40mgParticipants will take one 40 mg capsule of Pantoprazole daily for 5 days at the beginning of cycle 1 then they will take one capsule of matched Placebo daily for 5 days at the beginning of cycle 2
Placebo/PantoprazolePantoprazole 40mgParticipants will take one capsule of matched Placebo daily for 5 days at the beginning of cycle 1 then they will take one 40 mg capsule of Pantoprazole daily for 5 days at the beginning of cycle 2
Placebo/PantoprazolePlaceboParticipants will take one capsule of matched Placebo daily for 5 days at the beginning of cycle 1 then they will take one 40 mg capsule of Pantoprazole daily for 5 days at the beginning of cycle 2
Pantoprazole/PlaceboPlaceboParticipants will take one 40 mg capsule of Pantoprazole daily for 5 days at the beginning of cycle 1 then they will take one capsule of matched Placebo daily for 5 days at the beginning of cycle 2
Primary Outcome Measures
NameTimeMethod
Reduce the incidence of delayed CINV in patients receiving adjuvant or neoadjuvant breast cancer chemotherapyMeasured on day 5, after chemotherapy

To determine whether Pantoprazole can reduce the incidence of delayed CINV in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy (as measured on day 5 using the MASCC Antiemesis Tool (MAT) to assess nausea over days 2-5 of each chemotherapy cycle) as compared to placebo. Specifically, the primary endpoint will be the complete absence of both nausea and vomiting during days 2-5.

Secondary Outcome Measures
NameTimeMethod
Heartburn improvementDays 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)

Whether Pantoprazole improves heartburn score (measured using the FSSG for reflux and/or dyspepsia) as self-reported on day 5 regarding days 2-5.

Nausea MAT scoresDays 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)

Whether Pantoprazole improves nausea MAT scores over days 2-5

Vomiting MAT scoresDays 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)

Whether Pantoprazole reduces the number of episodes of vomiting (MAT) over days 2-5

Heartburn and Nausea scoresDays 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days), using a regression model, with allowance for a possible non-linear relationship.

Whether FSSG scores (heartburn) are associated with the MAT nausea scores reported by the patient over days 2-5.

Use of breakthrough medicationsDays 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)

Whether Pantoprazole lowers the requirement for breakthrough medications (as self-recorded by the patients on days 2-5).

Adverse eventsFrom date of consent to 28 days after the last study treatment

To assess whether adverse events (including hypomagnesemia, diarrhoea, abdominal pain and headache as defined by CT CAE version 4.03) are more common on Pantoprazole than on Placebo.

Patient preferenceend of chemotherapy cycle 2 (cycle 2 is either 14 or 21 days)

Whether Pantoprazole is preferred by patients over Placebo (by using a patient preference survey at the end of cycle 2).

Trial Locations

Locations (10)

Dunedin Hospital

🇳🇿

Dunedin, New Zealand

Waikato Hospital

🇳🇿

Hamilton, New Zealand

Rotorua Hospital

🇳🇿

Rotorua, New Zealand

Palmerston North Hospital

🇳🇿

Palmerston North, New Zealand

Auckland City Hospital

🇳🇿

Auckland, New Zealand

Christchurch Hospital

🇳🇿

Christchurch, New Zealand

Whangarei Hospital

🇳🇿

Whangarei, New Zealand

Wellington Hospital

🇳🇿

Wellington, New Zealand

Taranaki Base Hospital

🇳🇿

New Plymouth, New Zealand

Tauranga Hospital

🇳🇿

Tauranga, New Zealand

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