Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations
|ClinicalTrials.gov Identifier: NCT00977470|
Recruitment Status : Active, not recruiting
First Posted : September 15, 2009
Results First Posted : June 6, 2017
Last Update Posted : June 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer||Drug: Erlotinib Drug: Hydroxychloroquine||Phase 2|
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||76 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||May 2015|
|Estimated Study Completion Date :||December 2017|
Erlotinib 150 mg oral daily
150 mg taken orally once daily
Other Name: Tarceva
Experimental: Erlotinib and Hydroxychloroquine
Erlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily
150 mg taken orally once daily
Other Name: Tarceva
1000 mg taken orally once daily after erlotinib
Other Name: HCQ
- 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.
- Treatment Related Toxicity, > 10% Frequency, Any Grade [ Time Frame: 2 years ]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.
- Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ. [ Time Frame: 2 years ]
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
- Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ [ Time Frame: Until death ]
- Circulating Tumor Cell Quantification [ Time Frame: Until disease progression (median of 10.8 months) ]Serial circulating tumor cell (CTC) analyses will be performed on peripheral blood and correlated with disease response.
- EGFR Mutational Status [ Time Frame: 2 years ]Correlation of molecular and genetic tumor characteristics with disease response. Genomic DNA will be extracted from tumor tissue and direct sequencing analysis will be performed to identify additional mutations.
- Percent of Participants in Which FMISO-PET ([18F]-Fluoromisonidazole-positron Emission Tomography) is Able to Detect and Quantify Changes in Tumor Hypoxia After Erlotinib. [ Time Frame: 12 weeks ][18F]-FMISO-PET/CT was performed on a 64-slice PET/CT scanner and tracer uptake was assessed using SUV (standardized uptake value), normalizing the radioactivity measured in tissue by the injected dose and the body weight of the patient. Mean and maximum SUV and threshold volume of FMISO uptake were measured to quantify the extent of hypoxia in the primary tumor. Imaging was performed before and after initiation of therapy with erlotinib.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00977470
|United States, California|
|Stanford Cancer Institute|
|Stanford, California, United States, 94305|
|United States, Connecticut|
|Yale Cancer Center|
|New Haven, Connecticut, United States, 06519|
|United States, Maryland|
|University of Maryland|
|Baltimore, Maryland, United States, 21201|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Lecia Sequist, MD||Massachusetts General Hospital|