Non-small Cell Lung CancerPhase 2NCT00977470
Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations
A Phase 2 study testing Erlotinib and Hydroxychloroquine in people with Non-small Cell Lung Cancer, run by Massachusetts General Hospital at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Erlotinib and Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2009to Dec 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Maryland
Baltimore, Maryland, 21201
Massachusetts General Hospital
Boston, Massachusetts, 02114
Yale Cancer Center
New Haven, Connecticut, 06519
Stanford Cancer Institute
Stanford, California, 94305
About this study
Official title: Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations
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.
Read the detailed description
- 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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Erlotinib, Hydroxychloroquine
- Keywords
- NSCLC, HCQ, erlotinib, Tarceva
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
Also called Tarceva
150 mg taken orally once daily
Also called HCQ
1000 mg taken orally once daily after erlotinib
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib | Experimental | Erlotinib 150 mg oral daily Receives: Drug: Erlotinib |
| Erlotinib and Hydroxychloroquine | Experimental | Erlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily Receives: Drug: Erlotinib; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Nine months
Secondary outcomes (3)
Treatment Related Toxicity, > 10% Frequency, Any Grade
To evaluate the safety of treatment with erlotinib with and without hydroxychloroquine (HCQ). All participants receiving study treatment were evaluated for safety. Parameters included laboratory tests, hematological abnormalities, physical exam findings and spontaneous reports of adverse events reported by participants. Toxicities were evaluated and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = fatal.
Measured: 2 years
Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.
Response is assessed via spiral CT scan, done at baseline and after every 2 cycles of study treatment. Standard RECIST (Response Evaluation Criteria in Solid Tumors) was used. Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the size of target lesions, as compared to baseline; Progressive Disease (PD) = at least at 20% increase in the size of target lesions, or the appearance of one or more new lesions; Stable Disease (SD) = neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Response rate = CR + PR. Disease control rate = CR + PR + SD
Measured: 2 years
Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ
Measured: Until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2015
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University, Yale University, University of Maryland, Genentech, Inc.
- Responsible party
- Principal investigator, Lecia V. Sequist, Massachusetts General Hospital
- Investigators
- Lecia Sequist, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00977470
- Sponsor's protocol ID
- 09-097
- Other IDs
- OSI4620s
- Status last verified
- Sep 2025
- First submitted
- 11 Sep 2009
- Last updated
- 15 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25759424
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations
- ClinicalTrials.gov ID
- NCT00977470
- Acronym / sponsor ID
- 09-097
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- NSCLC, HCQ, erlotinib, Tarceva
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Stanford University, Yale University, University of Maryland, Genentech, Inc.
- Study start
- Oct 2009
- Primary completion
- May 2015 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 15 Sep 2009 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erlotinib | Experimental | Drug: ErlotinibErlotinib 150 mg oral daily |
| Erlotinib and Hydroxychloroquine | Experimental | Drug: Erlotinib, Drug: HydroxychloroquineErlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErlotinibAlso: Tarceva150 mg taken orally once daily | Drug | Erlotinib, Erlotinib and Hydroxychloroquine |
| HydroxychloroquineAlso: HCQ1000 mg taken orally once daily after erlotinib | Drug | Erlotinib and Hydroxychloroquine |
Primary outcome
Median Progression Free Survival
Time frame: From start of treatment until report of disease progression, assessed up to 10 years.
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.
Nine-month Progression-free Survival Rate
Time frame: Nine months
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.
3 secondary outcomes
Treatment Related Toxicity, > 10% Frequency, Any Grade
Time frame: 2 years
Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.
Time frame: 2 years
Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ
Time frame: Until death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25759424Arvold 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lecia Sequist, MD principal investigator
Massachusetts General Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erlotinib and Hydroxychloroquine in people with Non-small Cell Lung Cancer, run by Massachusetts General Hospital at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression Free Survival (time frame: From start of treatment until report of disease progression, assessed up to 10 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00977470, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2025.