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Report for Clinical Trial NCT00977470

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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.

NCT00977470 Non-small Cell Lung Cancer
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

2 Interventions

Name: Erlotinib

Description: 150 mg taken orally once daily
Type: Drug
Group Labels: 2

Erlotinib Erlotinib and Hydroxychloroquine

Name: Hydroxychloroquine

Description: 1000 mg taken orally once daily after erlotinib
Type: Drug
Group Labels: 1

Erlotinib and Hydroxychloroquine

Primary Outcomes

Description: 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.

Measure: Median Progression Free Survival

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

Description: 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.

Measure: Nine-month Progression-free Survival Rate

Time: Nine months

Secondary Outcomes

Description: 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.

Measure: Treatment Related Toxicity, > 10% Frequency, Any Grade

Time: 2 years

Description: 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

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

Time: 2 years

Measure: Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ

Time: Until death

Other Outcomes

Description: Serial circulating tumor cell (CTC) analyses will be performed on peripheral blood and correlated with disease response.

Measure: Circulating Tumor Cell Quantification

Time: Until disease progression (median of 10.8 months)

Description: 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.

Measure: EGFR Mutational Status

Time: 2 years

Description: [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.

Measure: 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: 12 weeks

Purpose: Treatment

Allocation: Randomized

Parallel Assignment

There are 2 SNPs


1 L858R

Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. --- L858R ---

2 T790M

Presence of the known resistance mutation T790M as detected by direct tumor sequencing is not allowed. --- T790M ---

HPO Nodes