Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations
Condition: Non-small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib; Hydroxychloroquine
Intervention description: 150 mg taken orally once daily; 1000 mg taken orally once daily after erlotinib
Intervention MeSH terms: Hydroxychloroquine; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC; HCQ; erlotinib; Tarceva

Summary:

      The purpose of this research study is to learn if adding hydroxychloroquine (HCQ) to
      erlotinib helps treat non-small cell lung cancer (NSCLC). Another goal of this research study
      is to learn more about NSCLC and how it may respond to study treatment. Erlotinib (Tarceva)
      is a type of drug called a tyrosine kinase inhibitor (TKI). TKIs block a protein called the
      epidermal growth factor receptor (EGFR). EGFR may control tumor growth and tumor cell
      survival. However, although TKI drugs can work for some lung cancer patients for a period of
      time, eventually the tumor finds a way to resist or counteract the TKI treatment and it
      begins to grow again. Hydroxychloroquine (HCQ) is a drug approved by the FDA for treating
      malaria, rheumatoid arthritis, and several other diseases. Laboratory research suggests that
      when HCQ is given with a TKI, it may help delay or prevent TKI resistance from developing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of non-small cell lung cancer

          -  Stage IV disease by the American Joint Committee on Cancer/IASLC 7th edition proposed
             edition staging criteria

          -  An EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients
             harboring the most common mutations, deletions in exon 19 or the L858R mutation in
             exon 21 are eligible. Presence of the known resistance mutation T790M as detected by
             direct tumor sequencing is not allowed. Other rare EGFR mutations may be eligible
             after discussion with the overall principal investigator

          -  Age equal to or greater than 18 years

          -  Measurable disease by RECIST criteria, defined as the presence of at least one lesion
             that can be accurately measured in at least one dimension (longest diameter to be
             recorded) as 10mm or greater with spiral CT scan

          -  ECOG Performance status of 0, 1 or 2

          -  Since prior radiation or surgery, 14 days or more must have elapsed before starting
             protocol treatment

          -  No prior treatment with erlotinib, gefitinib, or other small molecule EGFR-TKIs. Prior
             treatment in the adjuvant setting is allowed if at least 1 year has elapsed since TKI
             course.

          -  Adequate organ function as outlined in the protocol

          -  Patients must undergo a screening eye exam to obtain approval for HCQ treatment, which
             establishes the absence of baseline conditions include macular degeneration, visual
             field changes, other retinal disease, and cataracts that interfere with required
             funduscopic examinations

          -  No G6PD deficiency, as HCQ may cause hemolysis in patients with G6DP

        Exclusion Criteria:

          -  Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been
             definitively treated with radiation and/or surgery. Note that patients with a history
             of CNS metastases or cord compression are allowed if they have been definitively
             treated and are clinically stable. Maintenance steroids are allowed but maintenance
             seizure medication with an EIAED is not allowed

          -  Prior radiation therapy inclusive of all identified target lesions. Note that prior
             palliative radiation to bony disease, CNS disease, or a limited thoracic area is
             allowed, provided that there is measurable disease outside the field and radiation is
             completed at least two weeks prior to starting treatment and the patient has fully
             recovered from all side effects

          -  Current use of hydroxychloroquine for any reason

          -  Known hypersensitivity to chloroquine, hydroxychloroquine, or any closely related
             drug: erlotinib, gefitinib, or any closely related drug

          -  Patients who are pregnant or breastfeeding. Female subjects of childbearing potential
             and male subjects must practice acceptable methods of birth control

          -  Any evidence of clinically active interstitial lung disease. Note that patients with
             chronic, stable radiographic changes who are asymptomatic are eligible

          -  Invasive malignancies within the past 3 years except for adequately treated carcinoma
             of the cervix, basal or squamous cell carcinomas of the skin

          -  Evidence of any other significant clinical disorder or laboratory finding that makes
             it undesirable for the patient to participate in the study, including a prior
             diagnosis of porphyria or non-light-sensitive psoriasis, as HCQ can significantly
             exacerbate both of these conditions

          -  Use of any non-FDA approved or investigational agent in 30 days or less 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

          -  Life expectancy of less than 12 weeks