Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies
- 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.
|Carcinoma, Non-Small-Cell Lung Carcinoma, Small Cell Lung Carcinoma, Thymic||Drug: AZD6244 Drug: MK-2206 Drug: Lapatinib Drug: Erlotinib Drug: Sunitinib Procedure: Molecular Profiling||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Pilot Trial of Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies|
- To determine the feasibility of the use of tumor s molecular profiling and targeted therapies in the treatment of NSCLC, SCLC, and Thymic Malignancies [ Time Frame: 5 years ]
- To estimated the response rate of molecular-profile directed treatments in NSCLC, SCLC, and Thymic Malignancies [ Time Frame: 5 years ]
|Study Start Date:||January 21, 2011|
|Estimated Study Completion Date:||December 30, 2019|
|Estimated Primary Completion Date:||January 31, 2018 (Final data collection date for primary outcome measure)|
Active Comparator: A
150 mg/dayProcedure: Molecular Profiling
Active Comparator: B
75 mg BID by mouthProcedure: Molecular Profiling
Active Comparator: C
200 mg once weekly by mouthProcedure: Molecular Profiling
Active Comparator: D
1500 mg daily by mouthProcedure: Molecular Profiling
Active Comparator: E
50 mg daily by mouthProcedure: Molecular Profiling
NOS (not otherwise specified)
Procedure: Molecular Profiling
- A better understanding of the genetic make-up of the individual tumor may offer potentially improved therapies. This approach may also give rapid access to response data in patients with sometimes rare genetic abnormalities.
- In addition, it will allow us to test targeted therapies in a select population of patients that is more likely to have a favorable response based on their molecular profile and the specific mechanism of action of the drug being tested.
- This approach will also speed up drug development and potentially approval, and rescue an otherwise ineffective drug candidate for the specific subgroup that can benefit.
- To determine the feasibility of the use of tumor s molecular profiling and targeted therapies in the treatment of advanced stage non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and thymic malignancies.
- To estimate the response rate of molecular-profile directed treatments in NSCLC, SCLC and thymic malignancies patients.
- Patients with histologically confirmed advanced lung cancer or thymic malignancies for whom surgical resection with curative intent is not feasible.
- Patients must either have biopsiable disease and be willing to undergo biopsy for
molecular profiling or have paraffin embedded tissue blocks suitable for molecular
- Individuals are eligible for EGFR germline mutation testing if they have:
- a personal history of invasive lung cancer or one of the pre-invasive histologies
associated with the development of lung cancer and more than two affected family
- All patients will have their tumors undergo molecular profiling. Based on these results and on other eligibility criteria, the patients will be offered enrollment into different targeted therapy arms.
- At the NCI site only, individuals eligible for EGFR germline mutation will undergo testing for germline mutations affecting the EGFR gene; if a mutation is detected, their first-degree relatives would be invited to undergo testing for the index germline mutation found in the proband and appropriate follow-up on trial.
- Effective with Amendment I, the participating site, OHSU, will discontinue new enrollments and data entry for existing patients on the NOS arm on this protocol in favor of the OHSU protocol L8639, Personalized Cancer Medicine Registry. The data from these patients will be included with the data from 11-C-0096 (8639) NCI patients at the time of publication. Any OHSU patients who are eligible for a treatment arm will continue to be enrolled and followed per protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01306045
|Contact: Arlene W Berman, R.N.||(301) firstname.lastname@example.org|
|Contact: Udayan Guha, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Udayan Guha, M.D.||National Cancer Institute (NCI)|