Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies

Summary

Background:

\- The current standard of care for advanced lung cancer and cancers of the thymus consists primarily of chemotherapy treatment. The drugs used for chemotherapy depend on the classification of the cancer in different categories that are based on the appearance of the cancer in the microscope. Though this approach has been proved to be useful in some ways, the survival rates of individuals with lung cancer and cancers of the thymus are still very poor. Recent research has shown that several genetic abnormalities play an important role in the development and growth of lung cancer and cancers of the thymus, and that it is possible to improve treatment success rates with drugs that specifically target some of the abnormal genes. Researchers are interested in determining whether it is possible to analyze the genes of patients with lung cancer and cancers of the thymus in order to provide personalized treatment with drugs that target the specific gene abnormalities.

Objectives:

\- To evaluate the effectiveness of genetic analysis in determining targeted therapy for individuals with advanced non-small cell lung cancer, small cell lung cancer, and thymic cancer.

Eligibility:

\- Individuals at least 18 years of age who have been diagnosed with either lung cancer or a cancer of the thymus that is not considered to be curable with the use of surgery or radiation therapy.

Design:

* Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. Participants will have a tumor biopsy or provide previously collected tumor tissue for study.
* Based on the results of the tumor biopsy study, participants will be separated into different treatment groups:
* Participants with epidermal growth factor receptor (EGFR) gene mutation will receive a drug called erlotinib, which inhibits a protein called EGFR that is thought to be a key factor in the development and progression of some cancers.
* Participants with Kirsten rat sarcoma virus (KRAS), proto-oncogene B-Raf (BRAF), Harvey Rat sarcoma virus (HRAS), or NRAF gene mutations will receive a drug called AZD6244, which inhibits a protein called methyl ethyl ketone (MEK) that is thought to be a key factor in the development and progression of some cancers.
* Participants with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), protein kinase B (AKT), or phosphatase and tensin homolog (PTEN) gene mutations will receive a drug called MK-2206, which inhibits a protein called AKT that is thought to be a key factor in the development and progression of some cancers.
* Participants with KIT or platelet-derived growth factor receptor A, (PDGFRA) gene mutations will receive a drug called sunitinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers, including kidney cancer.
* Participants who have -erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene mutation or amplification will receive a drug called lapatinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers, including breast cancer.
* Participants who do not have any of the genetic abnormalities described above will be offered different options for treatment, including standard of care chemotherapy or treatment with investigational agents in a different research protocol.
* After 6 weeks of treatment, participants will have imaging studies to evaluate the status of their cancer. Treatment will continue as long as participants tolerate the drugs, and the disease does not progress.
* Participants who benefit from the first treatment but eventually develop resistance and progression of their cancer will be offered the chance to have a second tumor biopsy and undergo a different treatment for their cancer.

Conditions

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Small Cell Lung
• Carcinoma, Thymic

Interventions

DRUG

AZD6244

Cycle = 21 days AZD6244 Hydrogen Sulfate 75 mg by mouth (PO) every (Q) 12 Hours

DRUG

MK-2206

Cycle = 28 days MK-2206 200 mg by mouth (PO) every (Q) Week

DRUG

Lapatinib

Cycle = 21 days Lapatinib 1500 mg by mouth (PO) every day (QD)

DRUG

Erlotinib

Cycle = 21 days Erlotinib 150 mg by mouth (PO) every morning (QAM)

DRUG

Sunitinib

Cycle = 42 days Sunitinib 50 mg by mouth (PO) on days 1-28

PROCEDURE

Molecular Profiling

Molecular profiling of tumor tissue. Not Otherwise Specified (NOS) arm. Participants who do not meet the eligibility criteria for enrollment or who meet eligibility criteria for a particular arm but can't be enrolled

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Arun Rajan, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-02-08

Primary Completion

2014-02-12

Completion

2024-07-17

FDA Drug

Yes

Countries

• United States

Study Locations