Breast Cancer
Conditions
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.
Interventions
DRUGLansoprazole
administration of lansoprazole 60 mg twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles
DRUGPlacebo
administration of Placebo capsule twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | 6 months | \- Tumor response evaluation will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Change in ki67 level | 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. | \- 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 level | 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. | \- Assessment of P-gp level by ELISA Kits according to manufacturer's instructions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and toxicity | 6 months | \- Adverse events and toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5. |
| Follow up of complete blood count | baseline 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. |
| Follow up of kidney function | baseline 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 function | baseline 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. |
Countries
Egypt
Outcome results
None listed