Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: erlotinib; hydroxychloroquine
Intervention description: Taken orally once a day; Taken orally once a day
Intervention MeSH terms: Hydroxychloroquine; Erlotinib Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: erlotinib; tarceva; hydroxychloroquine; NSCLC

Summary:

      Erlotinib is a type of drug called a tyrosine kinase inhibitor (TKI). TKIs block a protein
      called epidermal growth factor receptor (EGFR). EGFR may control tumor growth and tumor cell
      survival. EGFR is found on the surface of many types of cancer cells, including non-small
      cell lung cancer (NSCLC). Erlotinib is approved by the Food and Drug Administration (FDA) for
      the treatment of NSCLC. Hydroxychloroquine (HCQ) is a drug approved by the FDA for treatment
      of malaria, rheumatoid arthritis, and several other diseases but is not currently thought of
      as a cancer treatment. Previous laboratory studies suggests that HCQ may have an anti-cancer
      effect by itself in some situations, particularly when EGFR TKI drugs have been useful in the
      past against the tumor. The two drugs together may be able to fight lung cancer in cases
      where erlotinib is no longer effective by itself. The purpose of this research study is to
      determine the highest dose of HCQ that can be given safely in combination with erlotinib. We
      will also begin to look at whether HCQ plus erlotinib helps treat cancer that have become
      resistant to TKI treatment after initially responding.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of non-small cell lung cancer

          -  Stage IIIB with pleural effusion or Stage IV disease by the American Joint Committee
             on Cancer (AJCC) 6th edition staging criteria.

          -  At least 12 weeks of prior treatment with erlotinib, gefitinib, or another EGFR small
             molecule TKI agent.

          -  Age equal to or greater than 18 years

          -  Measurable disease, defined according to RECIST criteria

          -  Performance status of 0, 1 or 2

          -  At least 2 weeks since prior radiation treatment

          -  At least 2 weeks since any prior chemotherapy or targeted therapy

          -  Adequate organ function as outlined in the protocol

          -  Approval for HCQ treatment by an eye doctor, based on a screening eye exam. Examples
             of disqualifying baseline conditions include macular degeneration and other retinal
             disease.

          -  Willingness to comply with protocol procedures including the blood-sampling schedule
             for PK analyses and periodic eye examination

        Exclusion Criteria:

          -  Current use of hydroxychloroquine for any reason

          -  Known hypersensitivity to chloroquine, hydroxychloroquine, or any other closely
             related drug

          -  Known hypersensitivity to erlotinib, gefitinib, or any closely related drug

          -  Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia
             in patients with G6PD deficiency

          -  Cataracts that would interfere with required funduscopic examinations, or severe
             baseline visual impairment including macular degeneration, retinopathy or visual field
             changes, or having only one functional eye. All patients must undergo a screening eye
             exam prior to enrollment

          -  Pregnancy or breastfeeding. Female subjects of childbearing age and male subjects must
             practice acceptable method of birth control

          -  Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been
             definitively treated with radiation and/or surgery

          -  Prior radiation therapy inclusive of all identified target lesions

          -  Any evidence of clinically active interstitial lung disease

          -  Malignancies within the past 3 years except for adequately treated carcinoma of the
             cervix or basal or squamous cell carcinomas of the skin

          -  Although not an absolute exclusion criteria, caution should be exercised in patients
             with a diagnosis of porphyria or non-light sensitive psoriasis, as HCQ can
             significantly exacerbate both of those conditions

          -  Evidence of any other significant clinical disorder or laboratory finding that makes
             it undesirable for the patient to participate in the study

          -  Use of any non-FDA approved or investigational agent within 2 weeks of enrolling onto
             the trial, or failure to recover from the side effects of any of these agents

          -  Penicillamine use for Wilson's disease or any other indication, as concomitant use
             with HCQ can increase toxicity to penicillamine