KRAS Gene Mutation, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Non-Small Cell Cancer AJCC v7
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDocetaxel
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGTrametinib
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* DISEASE RELATED CRITERIA: Patients must have pathologically confirmed KRAS mutation (at codon 12, 13 and 61) positive non-small cell lung cancer (NSCLC) that is stage IV or recurrent; the specific subtype of KRAS mutation must be known; KRAS mutation testing must have been performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; CLIA certified commercially available tests are acceptable * DISEASE RELATED CRITERIA: Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI) within 28 days prior to registration; the CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality; non-measurable disease must be assessed within 42 days prior to registration; all known sites of disease must be assessed and documented on the baseline tumor assessment form (Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]) * DISEASE RELATED CRITERIA: Patients must not have known brain metastases, leptomeningeal carcinomatosis or spinal cord compression unless: (1) metastases have been locally treated (including stereotactic body radiation therapy \[SBRT\], whole brain radiotherapy \[WBRT\], and surgical resection) and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 2 days prior to registration * PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have documented progressive cancer following at least one but no more than two prior regimens of systemic therapy for lung cancer, one of which must have been platinum based combination chemotherapy; treatment with an immune therapy or targeted therapy for advanced disease will be considered a separate regimen and will count toward the prior regimens; maintenance therapy will not be counted as a separate regimen; adjuvant chemotherapy or chemotherapy administered as part of concurrent chemotherapy and radiation therapy for the treatment of lung cancer will not count as a prior regimen of systemic therapy as long as recurrence of patient's lung cancer occurred more than 12 months after the last day of chemotherapy * PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have received any chemotherapy, biologic agent, or any investigational agent within 14 days prior to registration. Patients must have recovered from any adverse events to Common Terminology Criteria for Adverse Events (CTCAE) grade 0-1 prior to registration * PRIOR/CONCURRENT THERAPY CRITERIA: Prior treatment with an anti-PD-1 or anti-PDL1 is not required * PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have received prior docetaxel; patients must not have received therapy with a drug known to be either a mitogen-activated protein kinase (MEK) inhibitor or a phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitor * PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have recovered from any adverse effects from prior therapy (except alopecia) to =\< CTCAE grade 1 prior to registration * PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have had prior radiation therapy as long as it has not affected greater than 25% of the bone marrow and at least one measurable lesion is outside the area of prior radiation; at least 7 days must have elapsed since last radiation treatment; patients must have recovered from any adverse events from prior radiation therapy to =\< CTCAE grade 1 * PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have had a major surgery within 28 days prior to registration; patients must have recovered from any adverse effects of prior surgery to the satisfaction of the treating physician; biopsies and central IV access placement are not considered major surgery * PRIOR/CONCURRENT THERAPY CRITERIA: Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including but not limited to St. John's wort, kava, ephedra \[ma huang\], ginko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng) * CLINICAL/LABORATORY CRITERIA: Patients must have Zubrod performance status of 0-2 * CLINICAL/LABORATORY CRITERIA: Absolute neutrophil count (ANC) \>= 1500/mcL; these results must be obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Platelet count \>= 100,000/mcL; these results must be obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Hemoglobin \>= 9 grams/dl; these results must be obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN); these results must be obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (or =\< 5 x IULN for patients with known liver metastases); these results must be obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min; this result must have been obtained within 28 days prior to registration * CLINICAL/LABORATORY CRITERIA: Patients must be able to swallow oral medications and must not have a gastro-intestinal disorder with diarrhea as a major symptom or that may alter absorption such as malabsorption syndromes or gastric resection * CLINICAL/LABORATORY CRITERIA: Patient must not have prior history of interstitial lung disease or pneumonitis * CLINICAL/LABORATORY CRITERIA: Patients must not have history of significant co-morbid illness inclusive of but not restricted to New York Heart Association class II, congestive cardiac failure, uncontrolled hypertension, history of myocardial infarction, unstable angina, coronary angioplasty, stenting or cerebrovascular accident within 6 months prior to registration or any other illness that in the assessment of the treating physician would compromise the ability of the patient to participate in this study * CLINICAL/LABORATORY CRITERIA: Patients must have corrected QT (QTc) interval =\< 480 msec (using the Bazett's formula) on electrocardiogram (ECG) performed within 42 days prior to registration; history or evidence of current clinically significant uncontrolled arrhythmias are not eligible; however, patients with controlled atrial fibrillation for \> 30 days prior to randomization are eligible; patients must not have atrial fibrillation \> grade 2 on the screening ECG; patients with CTCAE grade 1-2 atrial fibrillation on their screening ECG must have a second ECG performed prior to registration and more than 30 days from the screening ECG (either before or after) with the most recent ECG showing stable or improving grade of atrial fibrillation * CLINICAL/LABORATORY CRITERIA: Patients must have a left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal (ILLN) by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) within 42 days prior to registration * CLINICAL/LABORATORY CRITERIA: Patients must not have untreated or unresolved retinopathy or have a history (or current evidence) of retinal vein occlusion determined by an ophthalmology exam within 42 days prior to registration * CLINICAL/LABORATORY CRITERIA: Patients must not have an immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients, or to dimethyl sulfoxide (DMSO) or other agents used in the study * CLINICAL/LABORATORY CRITERIA: Patients must not have a known history of active hepatitis B or C infection (defined as presence of hepatitis \[Hep\] B surface antigen \[sAg\] and/or Hep B deoxyribonucleic acid \[DNA\] and/or Hep C ribonucleic acid \[RNA\]); patients must not have a known history of human immunodeficiency virus (HIV) seropositivity * CLINICAL/LABORATORY CRITERIA: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years; patients with localized prostate cancer who are being followed by an active surveillance program are also eligible * CLINICAL/LABORATORY CRITERIA: Patients must not be pregnant or nursing due to the risk of fetal or nursing infant harm; women/men of reproductive potential must have agreed to use an effective contraceptive method (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation and for 4 months after the last dose of the drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * SPECIMEN SUBMISSION CRITERIA: Patients must be offered optional participation in banking of specimens for future research * REGULATORY CRITERIA: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * REGULATORY CRITERIA: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants | Up to 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation | Up to 3 years | 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 |
| Progression Free Survival in All KRAS Mutant Participants | Up to 3 years | 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. |
| Progression Free Survival in Participants With G12C KRAS Mutation | Up to 3 years | 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. |
| Progression Free Survival in Participants With Non-G12C KRAS Mutation | Up to 3 years | 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. |
| Overall Survival in All KRAS Mutants | Up to 3 years | Time from date of registration to date of death due to any cause. |
| Overall Survival in Participants With G12C KRAS Mutation | Up to 3 years | Time from date of registration to date of death due to any cause. |
| Overall Survival in Participants With Non-G12C KRAS Mutation | up to 3 years | Time from date of registration to date of death due to any cause. |
| Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation | up to 3 years | 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 |
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow up until death or 3 years post registration | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShirish M Gadgeel
SWOG Cancer Research Network
Participant flow
Pre-assignment details
60 participants were enrolled. However, 4 were found to be ineligible and 2 did not receive protocol treatment and so were not analyzable. Thus only 54 were included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Trametinib, Docetaxel) Participants receive trametinib PO on days 1-21. Participants also receive docetaxel IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Docetaxel: Given IV
Laboratory Biomarker Analysis: Correlative studies
Trametinib: Given PO | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | Treatment (Trametinib, Docetaxel) |
|---|---|
| Age, Continuous All Participants | 65 years |
| Age, Continuous Participants with G12C Mutation | 66 years |
| Age, Continuous Participants with Non-G12C Mutation | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Histology All Participants Adenocarcinoma | 48 Participants |
| Histology All Participants Other | 6 Participants |
| Histology Participants with G12C Mutation Adenocarcinoma | 17 Participants |
| Histology Participants with G12C Mutation Other | 2 Participants |
| Histology Participants with Non-G12C Mutation Adenocarcinoma | 31 Participants |
| Histology Participants with Non-G12C Mutation Other | 4 Participants |
| KRAS Mutation Type All Participants G12A | 9 Participants |
| KRAS Mutation Type All Participants G12C | 19 Participants |
| KRAS Mutation Type All Participants G12D | 9 Participants |
| KRAS Mutation Type All Participants G12F | 1 Participants |
| KRAS Mutation Type All Participants G12S | 2 Participants |
| KRAS Mutation Type All Participants G12V | 7 Participants |
| KRAS Mutation Type All Participants G13C | 4 Participants |
| KRAS Mutation Type All Participants G13D | 1 Participants |
| KRAS Mutation Type All Participants Q61K | 1 Participants |
| KRAS Mutation Type All Participants Q61L | 1 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12A | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12C | 19 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12D | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12F | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12S | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G12V | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G13C | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation G13D | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation Q61K | 0 Participants |
| KRAS Mutation Type Participants with G12C Mutation Q61L | 0 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12A | 9 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12C | 0 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12D | 9 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12F | 1 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12S | 2 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G12V | 7 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G13C | 4 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation G13D | 1 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation Q61K | 1 Participants |
| KRAS Mutation Type Participants with Non-G12C Mutation Q61L | 1 Participants |
| Metastic Sites at Baseline (Brain) All Participants | 7 Participants |
| Metastic Sites at Baseline (Brain) Participants with G12C Mutation | 4 Participants |
| Metastic Sites at Baseline (Brain) Participants with Non-G12C Mutation | 3 Participants |
| Metastic Sites at Baseline (Liver) All Participants | 17 Participants |
| Metastic Sites at Baseline (Liver) Participants with G12C Mutation | 8 Participants |
| Metastic Sites at Baseline (Liver) Participants with Non-G12C Mutation | 9 Participants |
| Prior Immunotherapy All Participants No | 23 Participants |
| Prior Immunotherapy All Participants Yes | 31 Participants |
| Prior Immunotherapy Participants with G12C Mutation No | 7 Participants |
| Prior Immunotherapy Participants with G12C Mutation Yes | 12 Participants |
| Prior Immunotherapy Participants with Non-G12C Mutation No | 16 Participants |
| Prior Immunotherapy Participants with Non-G12C Mutation Yes | 19 Participants |
| Prior Regimens All Participants 1 | 16 Participants |
| Prior Regimens All Participants 2 | 38 Participants |
| Prior Regimens Participants with G12C Mutation 1 | 6 Participants |
| Prior Regimens Participants with G12C Mutation 2 | 13 Participants |
| Prior Regimens Participants with Non-G12C Mutation 1 | 10 Participants |
| Prior Regimens Participants with Non-G12C Mutation 2 | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Sex: Female, Male All Participants Female | 31 Participants |
| Sex: Female, Male All Participants Male | 23 Participants |
| Sex: Female, Male Participants with G12C Mutation Female | 11 Participants |
| Sex: Female, Male Participants with G12C Mutation Male | 8 Participants |
| Sex: Female, Male Participants with Non-G12C Mutation Female | 20 Participants |
| Sex: Female, Male Participants with Non-G12C Mutation Male | 15 Participants |
| Smoking Status All Participants Current | 12 Participants |
| Smoking Status All Participants Former | 38 Participants |
| Smoking Status All Participants Never | 4 Participants |
| Smoking Status Participants with G12C Mutation Current | 2 Participants |
| Smoking Status Participants with G12C Mutation Former | 15 Participants |
| Smoking Status Participants with G12C Mutation Never | 2 Participants |
| Smoking Status Participants with Non-G12C Mutation Current | 10 Participants |
| Smoking Status Participants with Non-G12C Mutation Former | 23 Participants |
| Smoking Status Participants with Non-G12C Mutation Never | 2 Participants |
| Zubrod Performance Status All Participants 0 | 16 Participants |
| Zubrod Performance Status All Participants 1 | 37 Participants |
| Zubrod Performance Status All Participants 2 | 1 Participants |
| Zubrod Performance Status Participants with G12C Mutation 0 | 6 Participants |
| Zubrod Performance Status Participants with G12C Mutation 1 | 12 Participants |
| Zubrod Performance Status Participants with G12C Mutation 2 | 1 Participants |
| Zubrod Performance Status Participants with Non-G12C Mutation 0 | 10 Participants |
| Zubrod Performance Status Participants with Non-G12C Mutation 1 | 25 Participants |
| Zubrod Performance Status Participants with Non-G12C Mutation 2 | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 44 / 54 |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 31 / 54 |
Outcome results
Primary
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
Population: All eligible and analyzable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants | 0.33 proportion of participants |
Secondary
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
Population: Patients who received at least one dose of protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 5 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 4 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 4 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Conjunctivitis | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ejection fraction decreased | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Electrocardiogram QT corrected interval prolonged | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 8 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperkalemia | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypermagnesemia | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 3 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Left ventricular systolic dysfunction | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 5 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 4 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Multi-organ failure | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 3 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 4 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pericardial effusion | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 3 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 8 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash pustular | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Restrictive cardiomyopathy | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 6 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper gastrointestinal hemorrhage | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 1 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 2 Participants |
| Treatment (Trametinib, Docetaxel) | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound infection | 1 Participants |
Secondary
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
Population: All eligible and analyzable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Overall Survival in All KRAS Mutants | 10.9 months |
Secondary
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
Population: Eligible and analyzable participants with G12C KRAS mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Overall Survival in Participants With G12C KRAS Mutation | 8.8 months |
Secondary
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
Population: Eligible and analyzable participants with non-G12C KRAS mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Overall Survival in Participants With Non-G12C KRAS Mutation | 12.2 months |
Secondary
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
Population: All eligible and analyzable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Progression Free Survival in All KRAS Mutant Participants | 4.1 months |
Secondary
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
Population: Eligible and analyzable participants with G12C KRAS mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Progression Free Survival in Participants With G12C KRAS Mutation | 3.3 months |
Secondary
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
Population: Eligible and analyzable participants with non-G12C KRAS mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Progression Free Survival in Participants With Non-G12C KRAS Mutation | 4.1 months |
Secondary
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
Population: Eligible and analyzable participants with G12C KRAS mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation | 0.26 proportion of participants |
Secondary
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
Population: Eligible and analyzable participants with Non-G12C mutation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Trametinib, Docetaxel) | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation | 0.37 proportion of participants |
Other Pre-specified
Response Rates in the Presence of LKB1 Mutations
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.
Time frame: Up to 3 years
Other Pre-specified
Response Rates in the Presence of p53 Mutations
The response rate between patients with dysfunctional p53 will be compared to the response rate in patients without p53 dysfunction.
Time frame: Up to 3 years