Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02642042|
Recruitment Status : Active, not recruiting
First Posted : December 30, 2015
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|KRAS Gene Mutation Recurrent Lung Non-Small Cell Carcinoma Stage IV Non-Small Cell Lung Cancer AJCC v7||Drug: Docetaxel Other: Laboratory Biomarker Analysis Drug: Trametinib||Phase 2|
I. To evaluate the response rate (confirmed and unconfirmed) to trametinib plus docetaxel in the entire study population of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation positive non-small cell lung cancer (NSCLC) patients following one or two prior systemic therapies.
I. To evaluate if trametinib plus docetaxel is consistent with promise of activity measured by the response rate in G12C KRAS mutation positive NSCLC patients following one or two prior systemic therapies.
II. To assess the response rate of this combination in non-G12C KRAS mutation positive NSCLC patients.
III. To assess progression-free survival within the G12C and non-G12C KRAS positive subgroups and the entire study population.
IV. To evaluate the toxicity of the regimen. V. To assess overall survival within G12C positive patients, non-G12C positive patients, and the entire study population.
I. To evaluate the response rates in the presence of comutations p53 and LKB1. II. To bank specimens for future research.
Patients receive trametinib orally (PO) on days 1-21. Patients also receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Trametinib With Docetaxel in Patients With KRAS Mutation Positive Non-small Cell Lung Cancer (NSCLC) and Progressive Disease Following One or Two Prior Systemic Therapies|
|Actual Study Start Date :||July 18, 2016|
|Estimated Primary Completion Date :||October 15, 2020|
|Estimated Study Completion Date :||October 15, 2020|
Experimental: Treatment (trametinib, docetaxel)
Patients receive trametinib PO on days 1-21. Patients also receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations) [ Time Frame: Up to 3 years ]
- Response rate in patients with a G12C mutation [ Time Frame: Up to 3 years ]
- Progression free survival [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]Progression free survival estimates will be calculated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.
- Overall survival [ Time Frame: Up to 3 years ]Overall survival estimates will be calculated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.
- Incidence of toxicity graded according to the National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 3 years ]Toxicity rates can be estimated to within ± 14% with 95% confidence.
- Response rates in the presence of p53 mutations [ Time Frame: Up to 3 years ]The response rate between patients with dysfunctional p53 will be compared to the response rate in patients without p53 dysfunction.
- Response rates in the presence of LKB1 mutations [ Time Frame: Up to 3 years ]The response rate between patients with LKB1 disruption will be compared to the response rate in patients without LKB1 disruption. The response rate will be estimated by LKB1 disruption status (yes/no), along with 95% confidence intervals around the estimated proportions. This analysis will evaluate if disruption in LKB1 is associated with a lower probability of response.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02642042
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|Principal Investigator:||Shirish M Gadgeel||Southwest Oncology Group|