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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;



Recruitment Keyword(s)



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

Investigational Drug(s)


Investigational Device(s)



Drug: AZD6244
Drug: MK-2206
Drug: Lapatinib
Drug: Erlotinib
Drug: Sunitinib
Procedure/Surgery: Molecular Profiling

Supporting Site

National Cancer Institute


- 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.


- 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.


- 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.


- 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 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 KRAS, BRAF, HRAS, or NRAF gene mutations will receive a drug called AZD6244, which inhibits a protein called MEK that is thought to be a key factor in the development and progression of some cancers.

- Participants with PIK3CA, AKT, or 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 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 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.

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- Patients with histologically confirmed advanced NSCLC, SCLC and thymic malignancies for whom surgical resection or multimodality therapy with curative intent is not feasible. For patients with Stage III NSCLC, who can be encompassed by a radiation port, definitive XRT should have been performed first when possible.

- Individuals who meet the eligibility criteria for EGFR germline mutation testing but who do not have advanced cancer as defined in 3.1.1 may enroll for EGFR germline mutation testing only and will not be eligible for the treatment or NOS arms.

- Patients with advanced cancer must meet one of the following criteria (does not apply to firstdegree relatives or individuals with pre-invasive histology enrolling only for EGFR germline mutation testing):

--Patients must have biopsiable disease and be willing to undergo biopsy for molecular profiling


-Patients must have enough and adequate archival material from a previous biopsy to perform molecular profiling analyses. The adequacy of the material provided will be determined by the principal investigator in conjunction with the laboratories performing the molecular profiling analyses


-Patients must have previously undergone a successful molecular profiling of their tumor with mutation analysis of the genes described in section 5.2, as part of this protocol (crossover patients) or other molecular profiling protocols such as the Lung Cancer Mutation Consortium protocol among others.

- Age greater than or equal to18 years.


1. Patients who have had major surgery, chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.

2. Patients may not be receiving any other investigational agents or other medications for the treatment of their malignancy.

3. Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 1 week after the end of brain radiation may be enrolled to undergo molecular profiling at the discretion of the principal investigator. In addition, brain metastatic disease should be stable for at least 4 weeks, before the patients can be enrolled in any of the experimental treatment arms.

4. Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain tablets are excluded.

5. Any uncontrolled medical illness that precludes the patient from undergoing a biopsy for molecular profiling and / or receiving treatment under one of the experimental arms of the study should be excluded. These conditions include but are not limited to:

-Ongoing or uncontrolled, symptomatic congestive heart failure (Class III or IV as defined by the NYHA functional classification system (see Appendix D).

-Uncontrolled hypertension

-Unstable angina pectoris

-Cardiac arrhythmia

-Uncontrolled diabetes

-Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements.

6. Patients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant ECG abnormalities are excluded.

7. Caution should be used if patients are required to use a concomitant medication that can prolong the QT interval and efforts should be made to switch to a different medication before the patient begins treatment under an experimental arm. See Appendix E for a table of medications with the potential to prolong the QTc interval. A comprehensive list of agents with the potential to cause QTc prolongation can be found at:

8. The eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the Principal Investigator. (A list of potent CYP3A4 inducers or inhibitors can be found in Appendix F). Every effort should be made to switch patients taking such agents or substances to other medications before they begin treatment with one of the experimental drug included in this protocol, particularly patients with gliomas or brain metastases who are taking enzyme-inducing anticonvulsant agents. A comprehensive list of medications and substances known or with the potential to alter the pharmacokinetics of sunitinib through CYP3A4 is provided in Appendix F.

9. Patients with tumor amenable to potentially curative therapy as assessed by the investigator.

10. Pregnant women are excluded from this study because many of the FDA approved agents and investigational agents in this trial have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated in this protocol. These potential risks may also apply to other agents used in this study.

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Adjei AA, Cohen RB, Franklin W, Morris C, Wilson D, Molina JR, Hanson LJ, Gore L, Chow L, Leong S, Maloney L, Gordon G, Simmons H, Marlow A, Litwiler K, Brown S, Poch G, Kane K, Haney J, Eckhardt SG. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol. 2008 May 1;26(13):2139-46.

Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol. 2003 Oct;30(5 Suppl 16):105-16.

Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005 Nov 14;24(50):7455-64.

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Principal Investigator

Referral Contact

For more information:

Arun Rajan, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-5330D
(240) 760-6236

Corrine M. Keen, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D44B
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6097

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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