Clinical trial NCT04874935: The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer
Official title: The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2021-05-06
Enrollment: 66
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Tumor Response
timeFrame: 6 months
measure: Change in ki67 level
timeFrame: 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.
measure: Change in P-gp level
timeFrame: 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 outcomes:
measure: Adverse events and toxicity
timeFrame: 6 months
measure: Follow up of kidney function
timeFrame: baseline and monthly through study completion, an average of 4 to 6 months
measure: Follow up of liver function
timeFrame: baseline and monthly through study completion, an average of 4 to 6 months
measure: Follow up of complete blood count
timeFrame: baseline and monthly through study completion, an average of 4 to 6 months
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Faculty of Pharmacy
Study officials:
References:
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.
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.
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.
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.
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(1):85. doi: 10.1186/s13046-015-0194-x.
citation: 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.