Clinical trial NCT03948477: Pantoprazole Prophylaxis Against Delayed CINV for Patients Receiving Breast Cancer Chemotherapy
Official title: Phase II, Randomised, Double-blinded, Placebo Controlled, Crossover Trial to Assess Pantoprazole's Effectiveness as Prophylaxis Against Delayed CINV in Patients Receiving Adjuvant or Neoadjuvant Breast Cancer Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Oncology
Breast Cancer
Chemotherapy-induced Nausea and Vomiting
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blinded, randomised, crossover trial, phase II, stratified by the chemotherapy regimen
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

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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.

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Primary outcomes:
measure: Reduce the incidence of delayed CINV in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy
timeFrame: Measured on day 5, after chemotherapy
Secondary outcomes:
measure: Nausea MAT scores
timeFrame: Days 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)
measure: Vomiting MAT scores
timeFrame: Days 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)
measure: Heartburn improvement
timeFrame: Days 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)
measure: Heartburn and Nausea scores
timeFrame: Days 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.
measure: Use of breakthrough medications
timeFrame: Days 2-5 following chemotherapy for cycle 1 and 2 (each cycle is either 14 or 21 days)
measure: Patient preference
timeFrame: end of chemotherapy cycle 2 (cycle 2 is either 14 or 21 days)
measure: Adverse events
timeFrame: From date of consent to 28 days after the last study treatment
Other outcomes:
measure: Effect of chemotherapy regimen impacts use of Pantoprazole in terms of delayed CINV
timeFrame: Measured on day 5, after chemotherapy
measure: Cycle effect
timeFrame: Cycle 1 to end of cycle 2 (each cycle is either 14 or 21 days)
Locations:
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: New Plymouth
country: New Zealand
facility: Taranaki Base Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Rotorua
country: New Zealand
facility: Rotorua Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Whangarei
country: New Zealand
facility: Whangarei Hospital
Study officials:
affiliation: Midcentral Regional Cancer Centre Services
name: Ricard Isaacs, MBChB FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Midcentral Regional Cancer Centre Services
name: Navin Wewala, MBChB FRACP
role: PRINCIPAL_INVESTIGATOR
References: