Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (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.
Non-small Cell Lung Cancer
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Hydroxychloroquine With or Without Erlotinib in Advanced NSCLC|
- Identify the dose limiting toxicities and maximum tolerated dose of HCQ plus erlotinib in patients with advanced NSCLC and to determine the overall safety profile. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To determine the PK parameters of HCQ plus erlotinib. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To determine the objective tumor response rate to treatment with HCQ plus erlotinib. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To correlate EGFR mutations and EGFR amplification with response to treatment in patients with available tumor specimens. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
- 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.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Lecia Sequist, MD, MPH||Massachussets General Hospital|