Non-small Cell Lung CancerPhase 1NCT01026844
Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC)
A Phase 1 study testing erlotinib and hydroxychloroquine in people with Non-small Cell Lung Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial 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). 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
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Nov 2012
- Phase
- Phase 1
- 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 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Phase I Study of Hydroxychloroquine With or Without Erlotinib in Advanced NSCLC
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.
Read the detailed description
- The goal of this study is to find the highest dose of HCQ that can be given safely with erlotinib. Therefore, not all participants will receive the same dose of HCQ. Small groups of participants will be enrolled in steps in this trial. The first group will be given a certain dose of HCQ. If they have few or manageable side effects, the next small group of participants enrolled will receive a higher dose. This increase in doses will continue until the research doctors find the highest dose of HCQ that can be given without causing severe or unmanageable side effects.
- Both HCQ and erlotinib are pills that are taken orally. Treatment will be divided into time periods called cycles. Each treatment cycle is 28 days. The exception to this 28 day cycle is when participants start taking the pills for the first time. Erlotinib is started first for 7 days and then HCQ is added. When the HCQ begins, the first cycle of 28 days begins.
- There are several tests and procedures that will be performed at specific time periods during protocol treatment. These include: blood work, performance status assessment, questions about medical history and medications, tumor assessment with CT or MRI and, eye exams.
- Participants may continue to receive study treatment as long as they do not experience unacceptable side effects or disease progression.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- erlotinib, hydroxychloroquine
- Keywords
- erlotinib, tarceva, hydroxychloroquine, NSCLC
- 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
Taken orally once a day
Also called HCQ
Taken orally once a day
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib plus hydroxychloroquine | Experimental | erltoinib 150mg per day plus HCQ in esclating doses of 400mg, 600mg, 800mg and 1000mg per day Receives: Drug: erlotinib; Drug: hydroxychloroquine |
| Hydroxychloroqine | Experimental | hydroxychloroquine given at escalating doses of 400mg, 600mg, 800mg and 1000mg per day Receives: Drug: hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Describe the Number and Type of Observed Dose Limiting Toxcities
HCQ doses tested included 400mg, 600mg, 800mg, and 1000mg. Dose-limiting toxicities (DLTs) were defined as CTC of grade 2 or higher retinopathy or keratitis, or CTC of grade 3 or higher hematologic, skin, CNS, neuropathic, cardiac, respiratory, gastrointestinal, or renal AEs in the first cycle considered at least possibly related to HCQ. If a DLT was observed, an additional three patients were enrolled at that dose level. The maximum tolerated dose for HCQ in each arm would be defined as one dose level below that at which two or more of 6 patients experienced a DLT, or if no DLTs were observed, the highest tested dose.
Measured: 2 years
Secondary outcomes (3)
Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.
PK parameter tested was dose normalized minimum steady state concentration (Cmin SS) of HCQ in micromolar per gram. Note this outcome was only analyzed for the first 21 patients enrolled, 13 on erlotinib/HCQ and 8 on HCQ arm.
Measured: 2 years
Objective Tumor Response Rate
Number of Response Evaluation Criteria in Solid Tumors (RECIST) responses divided by number of patients treated. Per RECIST version 1.0 complete response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions. The objective tumor response rate is the CR + PR divided by the total number of patients
Measured: 2 years
Correlate Epidermal Growth Factor Receptor (EGFR) Mutations and EGFR Amplification With Response to Treatment in Patients With Available Tumor Specimens.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study startJul 2007
- Primary completionNov 2012
- Study completionNov 2012
Why it stopped: slow enrollment
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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Lecia V. Sequist, Massachusetts General Hospital
- Investigators
- Lecia Sequist, MD, MPH, Principal investigator, Massachussets General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01026844
- Sponsor's protocol ID
- 07-037
- Other IDs
- OSI4251s
- Status last verified
- Jan 2017
- First submitted
- 2 Dec 2009
- Last updated
- 30 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Goldberg SB, Supko JG, Neal JW, Muzikansky A, Digumarthy S, Fidias P, Temel JS, Heist RS, Shaw AT, McCarthy PO, Lynch TJ, Sharma S, Settleman JE, Sequist LV. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1602-8. doi: 10.1097/JTO.0b013e318262de4a.
PubMed 22878749
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Hydroxychloroquine With or Without Erlotinib in Advanced NSCLC
- ClinicalTrials.gov ID
- NCT01026844
- Acronym / sponsor ID
- 07-037
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- erlotinib, tarceva, hydroxychloroquine, NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrollment
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jul 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 4 Dec 2009 (estimated)
- Results
- Posted 31 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- The goal of this study is to find the highest dose of HCQ that can be given safely with erlotinib. Therefore, not all participants will receive the same dose of HCQ. Small groups of participants will be enrolled in steps in this trial. The first group will be given a certain dose of HCQ. If they have few or manageable side effects, the next small group of participants enrolled will receive a higher dose. This increase in doses will continue until the research doctors find the highest dose of HCQ that can be given without causing severe or unmanageable side effects.
- Both HCQ and erlotinib are pills that are taken orally. Treatment will be divided into time periods called cycles. Each treatment cycle is 28 days. The exception to this 28 day cycle is when participants start taking the pills for the first time. Erlotinib is started first for 7 days and then HCQ is added. When the HCQ begins, the first cycle of 28 days begins.
- There are several tests and procedures that will be performed at specific time periods during protocol treatment. These include: blood work, performance status assessment, questions about medical history and medications, tumor assessment with CT or MRI and, eye exams.
- Participants may continue to receive study treatment as long as they do not experience unacceptable side effects or disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erlotinib plus hydroxychloroquine | Experimental | Drug: erlotinib, Drug: hydroxychloroquineerltoinib 150mg per day plus HCQ in esclating doses of 400mg, 600mg, 800mg and 1000mg per day |
| Hydroxychloroqine | Experimental | Drug: hydroxychloroquinehydroxychloroquine given at escalating doses of 400mg, 600mg, 800mg and 1000mg per day |
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 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
Key exclusion criteria (14 listed)
- 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
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: TarcevaTaken orally once a day | Drug | Erlotinib plus hydroxychloroquine |
| hydroxychloroquineAlso: HCQTaken orally once a day | Drug | Erlotinib plus hydroxychloroquine, Hydroxychloroqine |
Primary outcome
Describe the Number and Type of Observed Dose Limiting Toxcities
Time frame: 2 years
HCQ doses tested included 400mg, 600mg, 800mg, and 1000mg. Dose-limiting toxicities (DLTs) were defined as CTC of grade 2 or higher retinopathy or keratitis, or CTC of grade 3 or higher hematologic, skin, CNS, neuropathic, cardiac, respiratory, gastrointestinal, or renal AEs in the first cycle considered at least possibly related to HCQ. If a DLT was observed, an additional three patients were enrolled at that dose level. The maximum tolerated dose for HCQ in each arm would be defined as one dose level below that at which two or more of 6 patients experienced a DLT, or if no DLTs were observed, the highest tested dose.
3 secondary outcomes
Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.
Time frame: 2 years
Objective Tumor Response Rate
Time frame: 2 years
Correlate Epidermal Growth Factor Receptor (EGFR) Mutations and EGFR Amplification With Response to Treatment in Patients With Available Tumor Specimens.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22878749Goldberg SB, Supko JG, Neal JW, Muzikansky A, Digumarthy S, Fidias P, Temel JS, Heist RS, Shaw AT, McCarthy PO, Lynch TJ, Sharma S, Settleman JE, Sequist LV. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1602-8. doi: 10.1097/JTO.0b013e318262de4a.
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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, MPH principal investigator
Massachussets General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib and hydroxychloroquine in people with Non-small Cell Lung Cancer, run by Massachusetts General Hospital at 1 site 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 14 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: stopped early, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 31 Jul 2013). 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?
Describe the Number and Type of Observed Dose Limiting Toxcities (time frame: 2 years). 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 NCT01026844, 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 30 Jan 2017.