Clinical trial NCT02232243: HCQ on PAR-4 Levels in Patients With Resectable Solid Tumors
Official title: A Pilot Study to Determine the Biological Effects of Hydroxychloroquine on PAR-4 Levels in Patients With Resectable Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Cancer
Surgery
Hydroxychloroquine
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2014-09-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Patients With Elevated Par-4 Levels
timeFrame: Baseline and day 14
measure: Optimal Biologic Dose of Hydroxychloroquine
timeFrame: Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky, Markey Cancer Center
state: Kentucky
Study officials:
affiliation: Lucille P. Markey Cancer Center at University of Kentucky
name: Peng Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.18632/genesandcancer.181.