Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild Type Advanced Non-Small Cell Lung Cancer (NSCLC) and a Randomized Phase II Study of AZD6244 With Erlotinib in Mutant KRAS Adva...

Summary

Background:

AZD6244 (ARRY-142886) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). Approximately 20% of lung cancers have KRAS mutations which can make some cancer treatments including erlotinib, a standard anticancer treatment drug less effective. Researchers are interested in determining whether AZD6244 is effective in treating advanced NSCLC (non small cell lung cancer), including KRAS mutated lung cancer that has not responded to standard therapy.

Objectives:

To determine the effectiveness of AZD6244, either alone or in combination with erlotinib, in preventing tumor growth in individuals with NSCLC.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with advanced NSCLC that has not responded to standard therapy.

Design:

* Participants will be screened with a medical history, physical examination, blood tests, imaging studies, and potentially, tumor biopsy tests to determine whether a participant's NSCLC contains mutations in the KRAS protein.
* Participants will be divided into two groups based on the status of the KRAS protein in their NSCLC tumor cells:
* Individuals with normal KRAS protein: Half will receive AZD6244 and erlotinib, and half will receive only erlotinib.
* Individuals with mutated KRAS protein: Half will receive AZD6244 and erlotinib, and half will receive only AZD6244.
* Participants will take their assigned medications daily (on an empty stomach in the morning and/or evening, depending on the treatment) for 28-day cycles of treatment. Participants will also keep a medication diary to record any side effects.
* Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers. Participants may also have an additional tumor biopsy after the end of the first treatment cycle.
* Treatment will continue until the disease progresses, significant side effects develop, the participant chooses to leave the study, or the researchers end the study....

Conditions

• Non Small Cell Lung Carcinoma

Interventions

DRUG

AZD6244

For KRAS mutant patients randomized to the single agent arm, AZD6244 75 mg bid (twice a day).

DRUG

Erlotinib

For Wild-Type KRAS patients randomized to the single agent arm, Erlotinib 150 mg qd (every day)

DRUG

AZD6244 + Erlotinib

For KRAS mutant patients and Wild-Type KRAS patients randomized to the combination arm (arms are stratified based on KRAS mutational status), AZD6244 150 mg qd (every day) + erl (erlotinib) mg qd.

Sponsors & Collaborators

• University of California, Davis

  collaborator OTHER

• University of Chicago

  collaborator OTHER

• University of Southern California

  collaborator OTHER

• City of Hope Medical Center

  collaborator OTHER

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

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

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-10-26

Primary Completion

2013-09-30

Completion

2015-11-21

FDA Drug

Yes

Countries

• United States

Study Locations