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Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations

Phase 2
18 Years
Open (Enrolling)
Non-small Cell Lung Cancer

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Trial Information

Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations

- Because no one knows which of the study options are best, participants will be
randomized into of the study groups: Group A (erlotinib) or Group B (erlotinib and
HCQ). Study treatment will be divided into time periods called cycles. Each study
treatment cycle is 28 days.

- Erlotinib (Group A and Group B) will be taken orally once a day. Hydroxychloroquine
(Group B) will be taken orally once a day after taking erlotinib.

- The following tests and procedures will be performed day 1 of each cycle: physical
examination, performance status assessment, questions about any symptoms or side
effects, blood for routine tests. The following procedures will be performed at
certain study visits: Research blood tests (cycle 1, cycle 2, then every other even
cycle); eye exam (cycle 4, cycle 7, and then every 3 months); assessment of the tumor
with CT or MRI scan (done at the end of even cycles.

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To demonstrate a difference in progression-free survival in patients with advanced NSCLC and EGFR mutations treated with erlotinib as compared with patients treated with erlotinib plus HCQ.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Lecia Sequist, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

October 2009

Completion Date:

December 2014

Related Keywords:

  • Non-Small Cell Lung Cancer
  • HCQ
  • erlotinib
  • Tarceva
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Yale Cancer Center New Haven, Connecticut  06520-8028
Massachusetts General Hospital Boston, Massachusetts  02114-2617
University of Maryland Baltimore, Maryland  21201
Stanford Cancer Institute Stanford, California  94305