HCQ on PAR-4 Levels in Patients With Resectable Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Pilot Study to Determine the Biological Effects of Hydroxychloroquine on PAR-4 Levels in Patients With Resectable Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02232243
• Other study ID #: 14-MULTI-14-MCC
• Status: Completed
• Phase: Phase 1
• Start date: July 2015
• Est. completion date: December 1, 2018

Study information

• Verified date: May 2019
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Baseline levels of PAR-4 secreted by normal cells are generally inadequate to cause massive apoptosis in cancer cells and drugs that bolster the secretion of PAR-4 would constitute an important therapeutic advance.The apoptosis sensitizing features of hydroxychloroquine enhance the anti-tumor effects of a broad range of cancer therapeutics. The investigators hypothesize that hydroxychloroquine will induce at least 2-fold increase in systemic (plasma) PAR-4 levels compared to pre-treatment plasma levels in patients with resectable solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 1, 2018
• Est. primary completion date: January 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have a histologically confirmed solid tumor that is planned for surgical resection.

• Age =18 years.

• ECOG performance status =2 (Karnofsky =60%, see Appendix A).

• Patients must be able to ingest oral medications.

• Patients must have normal organ and marrow function as defined below:

• absolute neutrophil count =1,500/mcL

• platelets =100,000/mcL

• total bilirubin Less than 1.5 x ULN

• AST(SGOT)/ALT(SGPT) =2.5 × institutional upper limit of normal

• Creatinine within normal institutional limits OR Creatinine clearance =60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

• Patients must be able to undergo surgical resection of their tumor as determined by the treating surgeon.

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients with metastatic cancer and/or cancer that is not amenable to surgery.

• Patients with significant malabsorption as determined by the treating physician.

• Patients who are receiving any other investigational agents.

• Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with primary brain tumors amenable to surgery are allowed on this protocol.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to hydroxychloroquine.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study.

• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with hydroxychloroquine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

• Patients that are on enzyme-inducing anti-epileptic medications

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Hydroxychloroquine, 200mg twice dailiy
Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.
• Hydroxychloroquine, 400mg twice daily
Hydroxychloroquine, 400mg twice daily (800mg/day total) was given to subjects for up to 14 days prior to surgery.

Locations

Country	Name	City	State
United States	University of Kentucky, Markey Cancer Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Peng Wang, MD PhD

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wang P, Burikhanov R, Jayswal R, Weiss HL, Arnold SM, Villano JL, Rangnekar VM. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018 May;9(5-6):190-197 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients With Elevated Par-4 Levels	Number of patients with 2-fold change in Par-4 levels from baseline to day 14	Baseline and day 14
Primary	Optimal Biologic Dose of Hydroxychloroquine	Dose (mg twice daily) wherein 70% of patients exhibit a 2-fold increase in Par-4 levels with a dose-limiting toxicity of no more than 30%.	Day 14