This phase II trial studies how well trametinib and docetaxel work in treating patients with stage IV KRAS mutation positive non-small cell lung cancer or cancer that has come back. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung cancer.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. TRANSLATIONAL MEDICINE OBJECTIVES: I. To evaluate the response rates in the presence of comutations p53 and LKB1. II. To bank specimens for future research. OUTLINE: Patients receive trametinib orally (PO) on days 1-21. Patients also receive docetaxel intravenously (IV) on day 1. Cycles 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
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Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants
Proportion of participants who have a partial or complete response to treatment per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 3 years
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation
Proportion of participants who have a partial or complete response to treatment per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 3 years
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation
Proportion of participants who have a partial or complete response to treatment per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: up to 3 years
Progression Free Survival in All KRAS Mutant Participants
Time 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 is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration.
Time frame: Up to 3 years
Progression Free Survival in Participants With G12C KRAS Mutation
Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration.
Time frame: Up to 3 years
Progression Free Survival in Participants With Non-G12C KRAS Mutation
Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration.
Time frame: Up to 3 years
Overall Survival in All KRAS Mutants
Time from date of registration to date of death due to any cause.
Time frame: Up to 3 years
Overall Survival in Participants With G12C KRAS Mutation
Time from date of registration to date of death due to any cause.
Time frame: Up to 3 years
Overall Survival in Participants With Non-G12C KRAS Mutation
Time from date of registration to date of death due to any cause.
Time frame: up to 3 years
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Duration of treatment and follow up until death or 3 years post registration
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