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

NCT02232243 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 14-MULTI-14-MCC
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor

Keywords

Cancer; Surgery; Hydroxychloroquine

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (3)

Initial: Hydroxychloroquine 400mg HCQ

EXPERIMENTAL

These initial 3 patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.

Drug: Hydroxychloroquine, 200mg twice dailiy

Secondary: Hydroxychloroquine 800mg HCQ

EXPERIMENTAL

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.

Drug: Hydroxychloroquine, 400mg twice daily

Tertiary: Hydroxychloroquine 400mg HCQ

EXPERIMENTAL

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.

Drug: Hydroxychloroquine, 200mg twice dailiy

Interventions

Hydroxychloroquine, 200mg twice dailiy DRUG

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

Initial: Hydroxychloroquine 400mg HCQ; Tertiary: Hydroxychloroquine 400mg HCQ

Hydroxychloroquine, 400mg twice daily DRUG

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

Secondary: Hydroxychloroquine 800mg HCQ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Peng Wang, MD PhD: lead

Study Sites (1)

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Related 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. doi: 10.18632/genesandcancer.181.

  PMID: 30603055 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Peng Wang
• Organization: University of Kentucky

p.wang@uky.edu

(859) 257-4488

Study Officials

• Peng Wang, MD, PhD

  Lucille P. Markey Cancer Center at University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 5, 2014
• Study Start: July 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: December 1, 2018
• Last Updated: June 28, 2021
• Results First Posted: July 23, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)