Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies
- Conditions
- Carcinoma, Non-Small-Cell LungCarcinoma, Small Cell LungCarcinoma, Thymic
- Interventions
- Drug: ErlotinibDrug: AZD6244Drug: MK-2206Drug: LapatinibDrug: SunitinibProcedure: Molecular Profiling
- Registration Number
- NCT01306045
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
- Detailed Description
BACKGROUND:
* 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.
Primary Objectives:
* To determine the feasibility of the use of tumors 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.
ELIGIBILITY:
* 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 profiling analysis.
* Individuals are eligible for epidermal growth factor receptor (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 members with invasive lung cancer or one of the pre-invasive histologies associated with the development of lung cancer,
OR
* a first-degree relative with a known EGFR germline mutation (EGFR exon 20 T790M, exon 21 V843I, exon 21 R831C and exon 20 R776G).
DESIGN:
* 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, Oregon Health and Science University (OHSU), will discontinue new enrollments and data entry for existing patients on the Not Other Specified (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) National Cancer Institute (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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 647
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A/ Erlotinib Erlotinib Arm A - Erlotinib 150 mg by mouth (PO) every morning (QAM) A/ Erlotinib Molecular Profiling Arm A - Erlotinib 150 mg by mouth (PO) every morning (QAM) B/ AZD6244 AZD6244 AZD6244 Hydrogen Sulfate 75 mg by mouth (PO) every (Q) 12 Hours B/ AZD6244 Molecular Profiling AZD6244 Hydrogen Sulfate 75 mg by mouth (PO) every (Q) 12 Hours C/ MK-2206 Molecular Profiling MK-2206 200 mg by mouth (PO) every (Q) Week D/ Lapatinib Molecular Profiling Lapatinib 1500 mg by mouth (PO) every day (QD) E/Sunitinib Molecular Profiling Sunitinib 50 mg by mouth (PO) on days 1-28 F/ Not Otherwise Specified (NOS) Molecular Profiling Participants who do not meet the eligibility criteria for enrollment C/ MK-2206 MK-2206 MK-2206 200 mg by mouth (PO) every (Q) Week D/ Lapatinib Lapatinib Lapatinib 1500 mg by mouth (PO) every day (QD) E/Sunitinib Sunitinib Sunitinib 50 mg by mouth (PO) on days 1-28
- Primary Outcome Measures
Name Time Method Percentage of Enrolled Participants Testing Positive for Genomic Abnormality 1 year and 11 months To determine the feasibility of the use of tumor molecular profiling and targeted therapies in the treatment of Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), and Thymic Malignancies, the trial will be evaluated by determining the percentage of enrolled participants with a genomic abnormality. Identifying molecular profiles may help identify new targeted treatments for cancer.
Number of Evaluable Participants With a Response Based on Molecular Profile Directed Treatments in Non-Small Cell Lung Cancer, (NSCLC), Small Cell Lung Cancer (SCLC), and Thymic Malignancies 1 year and 13 months Efficacy will be determined by assessing if participants who have treatment assigned on the basis of their molecular profiling results will exhibit reasonable response to the drug selected for their particular profile. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study Progressive Disease (PD) is At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
Percentage of Evaluable Participants Overall Response Rate (ORR) Based on the Drug Selected for Their Particular Profile 1 year and 13 months Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).Partial Response (PD) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study Progressive Disease (PD) is At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
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