The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer

Study Overview
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Brief Summary
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Investigation of the possible efficacy and safety of lansoprazole co-administration with neoadjuvant chemotherapy in tumor response in women with breast cancer who will be planned for surgery.

Detailed Description
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Several studies revealed that PPIs inhibit not only the H+/K+ ATPase in gastric parietal cells, but also the vacuolar H+ ATPase (V-ATPase) overexpressed in tumor cells, the V-ATPase is an ATP-dependent proton pump that transports H+ across both intracellular and plasma membranes to regulate intracellular and extracellular pH. Co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles which increase the sensitivity of the tumor cells to the anticancer agents. Moreover, the low extracellular pH induces an increased activity of drug efflux pumps P-glycoprotein (P-gp), which is closely associated with multi-drug resistance (MDR) of tumors. As a consequence, there remains a lower concentration of chemotherapeutic drugs in tumor cells and reduced cytotoxic efficacy, thus restoring the normal extracellular PH will decrease MDR.

Official Title
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The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females with age ≥ 18 years old. Newly diagnosed breast cancer patients. Planned neoadjuvant chemotherapy. Exclusion Criteria: Pregnancy. Nursing mothers. Active or uncontrolled infection. Presence of another malignancies. Inadequate blood picture. Serum Creatinine more than 1.5 mg /dl. AST and ALT more than 2.5 upper limit. History of known hypersensitivity to lansoprazole.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lansoprazole arm<br>33 patients who will receive neoadjuvant chemotherapy and lansoprazole 60 mg twice daily four days before starting chemotherapy regimen and then the same dose will be used during chemotherapy cycles | Drug: Lansoprazole<br>* administration of lansoprazole 60 mg twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles<br>|
| Placebo Comparator: Placebo arm<br>33 patients who will receive neoadjuvant chemotherapy and placebo capsules. | Drug: Placebo<br>* administration of Placebo capsule twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | - Tumor response evaluation will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 6 months | 
| Change in ki67 level | - Assessment of the level of Ki-67 expression in cancer cells through a staining process (a marker of cancer cell proliferation). | baseline and end of neoadjuvant chemotherapy cycles each cycle will be repeated every 21 days or may postponed according to patient condition and doctor instructions. | 
| Change in P-gp level | - Assessment of P-gp level by ELISA Kits according to manufacturer's instructions. | baseline and end of neoadjuvant chemotherapy cycles each cycle will be repeated every 21 days or may postponed according to patient condition and doctor instructions. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and toxicity | - Adverse events and toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5. | 6 months | 
| Follow up of kidney function | measurement of serum creatinine levels in (mg/dl) and blood urea nitrogen (BUN) levels in (mg/dl) from blood samples will be assessed monthly for all participants. | baseline and monthly through study completion, an average of 4 to 6 months | 
| Follow up of liver function | measurement of alanine transaminase (ALT) and aspartate transaminase (AST) both in U/L from blood samples will be assessed monthly for all participants. | baseline and monthly through study completion, an average of 4 to 6 months | 
| Follow up of complete blood count | measurement of the counts of red blood cells, white blood cells, platelets, hemoglobin and hematocrit will be assessed monthly for all participants. | baseline and monthly through study completion, an average of 4 to 6 months |