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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04874935
• Other study ID #: 34615/4/21
• Status: Completed
• Phase: Phase 3
• Start date: June 10, 2021
• Est. completion date: November 5, 2022

Study information

• Verified date: October 2022
• Source: Tanta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: November 5, 2022
• Est. primary completion date: November 5, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Lansoprazole
administration of lansoprazole 60 mg twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles
• Placebo
administration of Placebo capsule twice daily 4 days before starting neoadjuvant chemotherapy regimen and continue till end of chemotherapy cycles

Locations

Country	Name	City	State
Egypt	Faculty of Pharmacy	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (6)

da Silva VP, Mesquita CB, Nunes JS, de Bem Prunes B, Rados PV, Visioli F. Effects of extracellular acidity on resistance to chemotherapy treatment: a systematic review. Med Oncol. 2018 Oct 30;35(12):161. doi: 10.1007/s12032-018-1214-4. — View Citation

Ikemura K, Hiramatsu S, Okuda M. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy. Front Pharmacol. 2017 Dec 12;8:911. doi: 10.3389/fphar.2017.00911. eCollection 2017. Review. — View Citation

Lee YY, Jeon HK, Hong JE, Cho YJ, Ryu JY, Choi JJ, Lee SH, Yoon G, Kim WY, Do IG, Kim MK, Kim TJ, Choi CH, Lee JW, Bae DS, Kim BG. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget. 2015 Oct 27;6(33):35040-50. doi: 10.18632/oncotarget.5319. — View Citation

Lu ZN, Tian B, Guo XL. Repositioning of proton pump inhibitors in cancer therapy. Cancer Chemother Pharmacol. 2017 Nov;80(5):925-937. doi: 10.1007/s00280-017-3426-2. Epub 2017 Aug 31. Review. — View Citation

Wang BY, Zhang J, Wang JL, Sun S, Wang ZH, Wang LP, Zhang QL, Lv FF, Cao EY, Shao ZM, Fais S, Hu XC. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Exp Clin Cancer Res. 2015 Aug 22;34:85. doi: 10.1186/s13046-015-0194-x. Erratum in: J Exp Clin Cancer Res. 2015;34:109. — View Citation

Whitton B, Okamoto H, Packham G, Crabb SJ. Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer. Cancer Med. 2018 Aug;7(8):3800-3811. doi: 10.1002/cam4.1594. Epub 2018 Jun 21. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response	- Tumor response evaluation will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	6 months
Primary	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.
Primary	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	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
Secondary	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
Secondary	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
Secondary	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