Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations

NCT00977470 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: 09-097OSI4620s
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; HCQ; erlotinib; Tarceva

Outcome Measures

Primary Outcomes (2)

• Median Progression Free Survival

  A measure of progression-free survival in patients with advanced non small-cell lung cancer (NSCLC) and EGFR mutations treated with erlotinib as compared with patients treated with erlotinib plus hydroxychloroquine (HCQ). Disease progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, as seen on CT scan, or the appearance of one or more new lesions on CT scan.

  From start of treatment until report of disease progression, assessed up to 10 years.

• Nine-month Progression-free Survival Rate

  This trial can detect a difference in proportions alive without progression at 9 months from 50% in the erlotinib arm to 77% in the erlotinib plus hydroxychloroquine (HCQ) arm, using an alpha of 0.15 and power of 85%, using the two-sided Likelihood Ratio test. Progression is defined as at least a 20% increase in the size of existing lesions or the appearance of one or more new lesions.

  Nine months

Secondary Outcomes (3)

• Treatment Related Toxicity, > 10% Frequency, Any Grade

  2 years

• Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.

  2 years

• Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ

  Until death

Other Outcomes (3)

• Circulating Tumor Cell Quantification

  Until disease progression (median of 10.8 months)

• EGFR Mutational Status

  2 years

• Percent of Participants in Which FMISO-PET ([18F]-Fluoromisonidazole-positron Emission Tomography) is Able to Detect and Quantify Changes in Tumor Hypoxia After Erlotinib.

  12 weeks

Study Arms (2)

Erlotinib

EXPERIMENTAL

Erlotinib 150 mg oral daily

Drug: Erlotinib

Erlotinib and Hydroxychloroquine

EXPERIMENTAL

Erlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily

Drug: Erlotinib; Drug: Hydroxychloroquine

Interventions

Erlotinib DRUG

150 mg taken orally once daily

Also known as: Tarceva

Erlotinib; Erlotinib and Hydroxychloroquine

Hydroxychloroquine DRUG

1000 mg taken orally once daily after erlotinib

Also known as: HCQ

Erlotinib and Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Stanford University: collaborator
• Yale University: collaborator
• University of Maryland: collaborator
• Genentech, Inc.: collaborator

Study Sites (4)

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Arvold ND, Heidari P, Kunawudhi A, Sequist LV, Mahmood U. Tumor Hypoxia Response After Targeted Therapy in EGFR-Mutant Non-Small Cell Lung Cancer: Proof of Concept for FMISO-PET. Technol Cancer Res Treat. 2016 Apr;15(2):234-42. doi: 10.1177/1533034615574386. Epub 2015 Mar 10.

  PMID: 25759424 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines

Results Point of Contact

• Title: Maria Kempner
• Organization: Mass General Hospital Cancer Center

mkempner@partners.org

508-533-4132

Study Officials

• Lecia Sequist, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 15, 2009
• Study Start: October 1, 2009
• Primary Completion: May 1, 2015
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 15, 2025
• Results First Posted: June 6, 2017

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)