HCQ on PAR-4 Levels in Patients With Resectable Solid Tumors
Condition: Solid Tumor
MeSH terms: Neoplasms
Intervention: Hydroxychloroquine, 200mg twice dailiy; Hydroxychloroquine, 400mg twice daily
Intervention description: Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.; Hydroxychloroquine, 400mg twice daily (800mg/day total) was given to subjects for up to 14 days prior to surgery.
Intervention MeSH terms: Hydroxychloroquine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer; Surgery; Hydroxychloroquine

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