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

Phase 3
Completed
Conditions
Breast Cancer
Interventions
Drug: Placebo
Registration Number
NCT04874935
Lead Sponsor
Tanta University
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
66
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lansoprazole armLansoprazole33 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
Placebo armPlacebo33 patients who will receive neoadjuvant chemotherapy and placebo capsules.
Primary Outcome Measures
NameTimeMethod
Change in ki67 levelbaseline and end of neoadjuvant chemotherapy cycles each cycle will be repeated every 21 days or may postponed according to patient condition and doctor instructions.

- Assessment of the level of Ki-67 expression in cancer cells through a staining process (a marker of cancer cell proliferation).

Change in P-gp levelbaseline and end of neoadjuvant chemotherapy cycles each cycle will be repeated every 21 days or may postponed according to patient condition and doctor instructions.

- Assessment of P-gp level by ELISA Kits according to manufacturer's instructions.

Tumor Response6 months

- Tumor response evaluation will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures
NameTimeMethod
Follow up of kidney functionbaseline and monthly through study completion, an average of 4 to 6 months

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.

Follow up of liver functionbaseline and monthly through study completion, an average of 4 to 6 months

measurement of alanine transaminase (ALT) and aspartate transaminase (AST) both in U/L from blood samples will be assessed monthly for all participants.

Follow up of complete blood countbaseline and monthly through study completion, an average of 4 to 6 months

measurement of the counts of red blood cells, white blood cells, platelets, hemoglobin and hematocrit will be assessed monthly for all participants.

Adverse events and toxicity6 months

- Adverse events and toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.

Trial Locations

Locations (1)

Faculty of Pharmacy

🇪🇬

Tanta, Egypt

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