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Comparing Lung Cancer Targeted Therapies Based on KRAS Mutation Status

Name of the Trial

Randomized Phase II Study of AZD6244 MEK-Inhibitor and/or Erlotinib in KRAS Wild Type or Mutant KRAS Advanced Non-Small Cell Lung Cancer (NCI-10-C-0218). See the protocol summary.

Principal Investigator

Dr. Giuseppe Giaccone
Dr. Giuseppe Giaccone
Principal Investigator

Dr. Giuseppe Giaccone, NCI Center for Cancer Research   

Why This Trial Is Important

The anticancer drug erlotinib (Tarceva) is considered a standard therapy for patients with advanced non-small cell lung cancer (NSCLC) that has progressed after treatment with chemotherapy. Unfortunately, erlotinib has shown little benefit for NSCLC patients whose tumors have a mutated form of the gene KRAS; about 20 percent of NSCLC patients in the United States have tumors with KRAS mutations. Therefore, doctors are interested in finding other treatments that may help patients with KRAS-mutated NSCLC.

An experimental drug called AZD6244 (selumetinib) blocks the activity of a protein known as MEK, which is a critical component of a molecular pathway that is overactive in some patients with NSCLC. The protein product of the KRAS gene and another protein called EGFR, which is the molecular target of erlotinib, are both upstream components of the same molecular pathway. Early studies suggest AZD6244 may be active in patients with either mutated or normal (wild-type) KRAS genes.

In this trial, investigators will test the KRAS mutation status of tumors in patients with advanced NSCLC whose disease has progressed during or after chemotherapy, or who have refused chemotherapy. Those with wild-type KRAS tumors will be randomly assigned to receive either AZD6244 plus erlotinib or erlotinib alone, whereas those with mutated KRAS tumors will be randomly assigned to receive either AZD6244 plus erlotinib or AZD6244 alone.

Doctors want to know if AZD6244 will help patients live longer without further cancer progression. They will also monitor the patients to assess the safety and tolerability of AZD6244 alone and in combination with erlotinib and to determine whether any of the treatments improves overall survival in these patients.

“There really aren’t any good treatment options for non-small cell lung cancer patients with mutations in KRAS,” said Dr. Giaccone. “Because the experimental drug blocks a target downstream of EGFR, we think there may possibly be some synergy between AZD6244 and erlotinib.

“We have enrolled about 25 patients in the study so far and they have been tolerating the medications quite well, although there have been some side effects, such as diarrhea,” Dr. Giaccone added.

Patients in the study will take AZD6244 twice a day and/or erlotinib once a day and will be required to keep a medication log of their side effects. They will also undergo blood tests and imaging tests, and may undergo additional biopsies of their tumors. Treatment will continue in 28-day cycles until the patient’s cancer progresses, the patient experiences unacceptable toxicity, the patient decides to leave the study, or the study is terminated.

For More Information

See the lists of entry criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

  • Posted: August 9, 2011