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

NCT ID: NCT02232243

Last Updated: 2021-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-12-01

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Initial: Hydroxychloroquine 400mg HCQ

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

Group Type: EXPERIMENTAL

Hydroxychloroquine, 200mg twice dailiy

Intervention Type: DRUG

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

Secondary: Hydroxychloroquine 800mg HCQ

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.

Group Type: EXPERIMENTAL

Hydroxychloroquine, 400mg twice daily

Intervention Type: DRUG

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

Tertiary: Hydroxychloroquine 400mg HCQ

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.

Group Type: EXPERIMENTAL

Hydroxychloroquine, 200mg twice dailiy

Intervention Type: DRUG

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

Interventions

Hydroxychloroquine, 200mg twice dailiy

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

Intervention Type: DRUG

Hydroxychloroquine, 400mg twice daily

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peng Wang, MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Peng Wang, MD PhD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peng Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lucille P. Markey Cancer Center at University of Kentucky

Locations

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 30603055 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

14-MULTI-14-MCC

Identifier Type: -

Identifier Source: org_study_id