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

Phase 1

Completed

• Conditions: Solid Tumor
• Interventions: Drug: Hydroxychloroquine, 200mg twice dailiy; Drug: Hydroxychloroquine, 400mg twice daily

• Registration Number: NCT02232243
• Lead Sponsor: Peng Wang, MD PhD

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-09-02
• Study First Submitted QC: 2014-09-04
• Study First Posted: 2014-09-05
• Study Start: 2015-07
• Primary Completion: 2018-01-01
• Study Completion: 2018-12-01
• Status Verified: 2019-05
• Results First Submitted: 2019-05-21
• Results First Submitted QC: 2019-05-21
• Results First Posted: 2019-07-23
• Last Update Submitted: 2021-06-03
• Last Update Posted: 2021-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Initial: Hydroxychloroquine 400mg HCQ	Hydroxychloroquine, 200mg twice dailiy	These initial 3 patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.
Secondary: Hydroxychloroquine 800mg HCQ	Hydroxychloroquine, 400mg twice daily	Based on data analysis from the initial patients, these patients received 400mg hydroxychloroquine (HCQ) twice daily (800mg/day total) for 14 days prior to surgery.
Tertiary: Hydroxychloroquine 400mg HCQ	Hydroxychloroquine, 200mg twice dailiy	Based on data from the primary and secondary groups, patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.

Primary Outcome Measures

Name	Time	Method
Patients With Elevated Par-4 Levels	Baseline and day 14	Number of patients with 2-fold change in Par-4 levels from baseline to day 14
Optimal Biologic Dose of Hydroxychloroquine	Day 14	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%.

Trial Locations

Locations (1)

University of Kentucky, Markey Cancer Center; 🇺🇸 Lexington, Kentucky, United States