Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT02642042
• Recruitment Status: Active, not recruiting
• First Posted: December 30, 2015
• Results First Posted: February 2, 2021
• Last Update Posted: May 3, 2023
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: KRAS Gene Mutation; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7
• Interventions: Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Trametinib
• Enrollment: 60

Participant Flow

Recruitment Details
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.

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description	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
Period Title: Overall Study
Started	54
Completed	0
Not Completed	54
Reason Not Completed
Adverse Event	22
Refusal Unrelated to Adverse Event	1
Progression/Relapse	28
Death	1
Not Protocol Specified	2

Baseline Characteristics

Arm/Group Title		Treatment (Trametinib, Docetaxel)
Arm/Group Description		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
Overall Number of Baseline Participants		54
Baseline Analysis Population Description		Eligible and analyzable participants
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
All Participants	Number Analyzed	54 participants
		65; (47 to 78)
Participants with G12C Mutation	Number Analyzed	19 participants
		66; (47 to 78)
Participants with Non-G12C Mutation	Number Analyzed	35 participants
		63; (48 to 77)
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	Female	31 57.4%
	Male	23 42.6%
Participants with G12C Mutation	Number Analyzed	19 participants
	Female	11 57.9%
	Male	8 42.1%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	Female	20 57.1%
	Male	15 42.9%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	53 98.1%
	Unknown or Not Reported	1 1.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 3.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	5 9.3%
	White	46 85.2%
	More than one race	0 0.0%
	Unknown or Not Reported	1 1.9%
Smoking Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	Current	12 22.2%
	Former	38 70.4%
	Never	4 7.4%
Participants with G12C Mutation	Number Analyzed	19 participants
	Current	2 10.5%
	Former	15 78.9%
	Never	2 10.5%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	Current	10 28.6%
	Former	23 65.7%
	Never	2 5.7%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Zubrod Performance Status [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	0	16 29.6%
	1	37 68.5%
	2	1 1.9%
Participants with G12C Mutation	Number Analyzed	19 participants
	0	6 31.6%
	1	12 63.2%
	2	1 5.3%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	0	10 28.6%
	1	25 71.4%
	2	0 0.0%
		[1] Measure Description: Participants are graded according to the Zubrod Performance Status Scale, which runs from 0 to 5, with 0 denoting perfect health and 5 death 0 - fully active, able to carryout pre-disease performance without restriction; - restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework or office work; - ambulatory and capable of self-care but unable to carry out work activities; up and about more than 50% of waking hours; [2] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Histology [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	Adenocarcinoma	48 88.9%
	Other	6 11.1%
Participants with G12C Mutation	Number Analyzed	19 participants
	Adenocarcinoma	17 89.5%
	Other	2 10.5%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	Adenocarcinoma	31 88.6%
	Other	4 11.4%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Metastic Sites at Baseline (Liver) [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
		17 31.5%
Participants with G12C Mutation	Number Analyzed	19 participants
		8 42.1%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
		9 25.7%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Metastic Sites at Baseline (Brain) [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
		7 13.0%
Participants with G12C Mutation	Number Analyzed	19 participants
		4 21.1%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
		3 8.6%
		[1] Measure Analysis Population Description: Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Prior Regimens [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	1	16 29.6%
	2	38 70.4%
Participants with G12C Mutation	Number Analyzed	19 participants
	1	6 31.6%
	2	13 68.4%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	1	10 28.6%
	2	25 71.4%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
Prior Immunotherapy [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	Yes	31 57.4%
	No	23 42.6%
Participants with G12C Mutation	Number Analyzed	19 participants
	Yes	12 63.2%
	No	7 36.8%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	Yes	19 54.3%
	No	16 45.7%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).
KRAS Mutation Type [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Participants	Number Analyzed	54 participants
	G12A	9 16.7%
	G12C	19 35.2%
	G12D	9 16.7%
	G12F	1 1.9%
	G12S	2 3.7%
	G12V	7 13.0%
	G13C	4 7.4%
	G13D	1 1.9%
	Q61K	1 1.9%
	Q61L	1 1.9%
Participants with G12C Mutation	Number Analyzed	19 participants
	G12A	0 0.0%
	G12C	19 100.0%
	G12D	0 0.0%
	G12F	0 0.0%
	G12S	0 0.0%
	G12V	0 0.0%
	G13C	0 0.0%
	G13D	0 0.0%
	Q61K	0 0.0%
	Q61L	0 0.0%
Participants with Non-G12C Mutation	Number Analyzed	35 participants
	G12A	9 25.7%
	G12C	0 0.0%
	G12D	9 25.7%
	G12F	1 2.9%
	G12S	2 5.7%
	G12V	7 20.0%
	G13C	4 11.4%
	G13D	1 2.9%
	Q61K	1 2.9%
	Q61L	1 2.9%
		[1] Measure Analysis Population Description: Eligible and analyzable participants were stratified based on whether they had G12C mutation or non-G12C mutations. Baseline measures are reported in separate rows for all participants (54), participants with G12C mutation (19), and participants with non-G12C mutations (35).

Outcome Measures

1. Primary Outcome

Title	Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants
Description	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

Outcome Measure Data

Analysis Population Description

All eligible and analyzable participants

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	54
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.33; (0.21 to 0.47)

2. Secondary Outcome

Title	Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with G12C KRAS mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.26; (0.09 to 0.51)

3. Secondary Outcome

Title	Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with Non-G12C mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.37; (0.21 to 0.55)

4. Secondary Outcome

Title	Progression Free Survival in All KRAS Mutant Participants
Description	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

Outcome Measure Data

Analysis Population Description

All eligible and analyzable participants

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	54
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	4.1; (3.1 to 5.1)

5. Secondary Outcome

Title	Progression Free Survival in Participants With G12C KRAS Mutation
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with G12C KRAS mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	3.3; (1.5 to 4.3)

6. Secondary Outcome

Title	Progression Free Survival in Participants With Non-G12C KRAS Mutation
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with non-G12C KRAS mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	4.1; (3.4 to 5.6)

7. Secondary Outcome

Title	Overall Survival in All KRAS Mutants
Description	Time from date of registration to date of death due to any cause.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable participants

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	54
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	10.9; (8.0 to 14.0)

8. Secondary Outcome

Title	Overall Survival in Participants With G12C KRAS Mutation
Description	Time from date of registration to date of death due to any cause.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with G12C KRAS mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	8.8; (4.9 to 10.9)

9. Secondary Outcome

Title	Overall Survival in Participants With Non-G12C KRAS Mutation
Description	Time from date of registration to date of death due to any cause.
Time Frame	up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants with non-G12C KRAS mutation

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	12.2; (8.0 to 18.8)

10. Secondary Outcome

Title	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	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

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of protocol treatment.

Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description:	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
Overall Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: Participants
Abdominal pain	1
Alanine aminotransferase increased	1
Anemia	4
Anorexia	2
Aspartate aminotransferase increased	2
Colitis	1
Conjunctivitis	1
Dehydration	2
Diarrhea	5
Dyspnea	4
Ejection fraction decreased	1
Electrocardiogram QT corrected interval prolonged	1
Fatigue	8
Febrile neutropenia	2
Gastrointestinal disorders - Other, specify	2
Generalized muscle weakness	1
Hyperkalemia	2
Hypermagnesemia	1
Hypokalemia	2
Hyponatremia	3
Hypotension	2
Hypoxia	1
Left ventricular systolic dysfunction	1
Lung infection	5
Lymphocyte count decreased	1
Mucositis oral	4
Multi-organ failure	1
Myocardial infarction	1
Nausea	3
Neutrophil count decreased	4
Palmar-plantar erythrodysesthesia syndrome	1
Pericardial effusion	1
Peripheral sensory neuropathy	1
Pneumonitis	2
Pruritus	2
Rash acneiform	3
Rash maculo-papular	8
Rash pustular	1
Respiratory failure	2
Restrictive cardiomyopathy	1
Sepsis	6
Stroke	1
Thromboembolic event	2
Upper gastrointestinal hemorrhage	1
Urinary tract infection	1
Vomiting	2
White blood cell decreased	2
Wound infection	1

11. Other Pre-specified Outcome

Title	Response Rates in the Presence of p53 Mutations
Description	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

Outcome Measure Data Not Reported

12. Other Pre-specified Outcome

Title	Response Rates in the Presence of LKB1 Mutations
Description	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

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Duration of treatment and follow up until death or 3 years post registration
Adverse Event Reporting Description	54 participants who were eligible and received protocol therapy were assessed for AEs.
Arm/Group Title	Treatment (Trametinib, Docetaxel)
Arm/Group Description	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
All-Cause Mortality
	Treatment (Trametinib, Docetaxel)
	Affected / at Risk (%)
Total	44/54 (81.48%)
Serious Adverse Events
	Treatment (Trametinib, Docetaxel)
	Affected / at Risk (%)
Total	31/54 (57.41%)
Blood and lymphatic system disorders
Anemia †	1/54 (1.85%)
Febrile neutropenia †	2/54 (3.70%)
Cardiac disorders
Myocardial infarction †	1/54 (1.85%)
Pericardial effusion †	1/54 (1.85%)
Sinus tachycardia †	1/54 (1.85%)
Gastrointestinal disorders
Abdominal pain †	1/54 (1.85%)
Diarrhea †	2/54 (3.70%)
Gastric hemorrhage †	1/54 (1.85%)
Gastrointestinal disorders-Other †	2/54 (3.70%)
Lower gastrointestinal hemorrhage †	1/54 (1.85%)
Mucositis oral †	1/54 (1.85%)
Nausea †	1/54 (1.85%)
Upper gastrointestinal hemorrhage †	1/54 (1.85%)
Vomiting †	2/54 (3.70%)
General disorders
Fatigue †	1/54 (1.85%)
Fever †	1/54 (1.85%)
Infections and infestations
Lung infection †	7/54 (12.96%)
Sepsis †	5/54 (9.26%)
Urinary tract infection †	1/54 (1.85%)
Wound infection †	1/54 (1.85%)
Investigations
Aspartate aminotransferase increased †	1/54 (1.85%)
Ejection fraction decreased †	1/54 (1.85%)
Weight loss †	1/54 (1.85%)
Metabolism and nutrition disorders
Anorexia †	2/54 (3.70%)
Dehydration †	2/54 (3.70%)
Hyperglycemia †	1/54 (1.85%)
Hypokalemia †	1/54 (1.85%)
Musculoskeletal and connective tissue disorders
Flank pain †	1/54 (1.85%)
Generalized muscle weakness †	2/54 (3.70%)
Nervous system disorders
Stroke †	2/54 (3.70%)
Psychiatric disorders
Confusion †	1/54 (1.85%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage †	1/54 (1.85%)
Dyspnea †	2/54 (3.70%)
Hypoxia †	1/54 (1.85%)
Pleural effusion †	2/54 (3.70%)
Pneumonitis †	2/54 (3.70%)
Respiratory failure †	2/54 (3.70%)
Vascular disorders
Hypertension †	1/54 (1.85%)
Hypotension †	2/54 (3.70%)
Thromboembolic event †	3/54 (5.56%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Trametinib, Docetaxel)
	Affected / at Risk (%)
Total	54/54 (100.00%)
Blood and lymphatic system disorders
Anemia †	27/54 (50.00%)
Blood and lymphatic system disorders - Other †	1/54 (1.85%)
Thrombotic thrombocytopenic purpura †	1/54 (1.85%)
Cardiac disorders
Atrial fibrillation †	1/54 (1.85%)
Cardiac disorders-Other †	1/54 (1.85%)
Left ventricular systolic dysfunction †	1/54 (1.85%)
Pericardial effusion †	1/54 (1.85%)
Restrictive cardiomyopathy †	1/54 (1.85%)
Sinus bradycardia †	1/54 (1.85%)
Sinus tachycardia †	7/54 (12.96%)
Ventricular arrhythmia †	1/54 (1.85%)
Ear and labyrinth disorders
Ear pain †	1/54 (1.85%)
External ear inflammation †	1/54 (1.85%)
Tinnitus †	1/54 (1.85%)
Vertigo †	1/54 (1.85%)
Endocrine disorders
Adrenal insufficiency †	1/54 (1.85%)
Eye disorders
Blurred vision †	5/54 (9.26%)
Conjunctivitis †	2/54 (3.70%)
Dry eye †	1/54 (1.85%)
Eye disorders-Other †	4/54 (7.41%)
Glaucoma †	1/54 (1.85%)
Watering eyes †	5/54 (9.26%)
Gastrointestinal disorders
Abdominal pain †	13/54 (24.07%)
Anal pain †	1/54 (1.85%)
Bloating †	3/54 (5.56%)
Colitis †	1/54 (1.85%)
Colonic obstruction †	1/54 (1.85%)
Constipation †	22/54 (40.74%)
Dental caries †	1/54 (1.85%)
Diarrhea †	39/54 (72.22%)
Dry mouth †	7/54 (12.96%)
Dyspepsia †	3/54 (5.56%)
Dysphagia †	2/54 (3.70%)
Flatulence †	3/54 (5.56%)
Gastroesophageal reflux disease †	3/54 (5.56%)
Gastrointestinal disorders-Other †	6/54 (11.11%)
Mucositis oral †	18/54 (33.33%)
Nausea †	32/54 (59.26%)
Oral hemorrhage †	2/54 (3.70%)
Oral pain †	2/54 (3.70%)
Stomach pain †	1/54 (1.85%)
Vomiting †	16/54 (29.63%)
General disorders
Chills †	4/54 (7.41%)
Edema face †	3/54 (5.56%)
Edema limbs †	19/54 (35.19%)
Fatigue †	44/54 (81.48%)
Fever †	12/54 (22.22%)
Flu like symptoms †	1/54 (1.85%)
General disorders and admin site conditions - Other †	4/54 (7.41%)
Infusion related reaction †	1/54 (1.85%)
Malaise †	1/54 (1.85%)
Multi-organ failure †	1/54 (1.85%)
Neck edema †	1/54 (1.85%)
Non-cardiac chest pain †	3/54 (5.56%)
Pain †	2/54 (3.70%)
Infections and infestations
Bronchial infection †	1/54 (1.85%)
Infections and infestations-Other †	4/54 (7.41%)
Laryngitis †	1/54 (1.85%)
Lung infection †	1/54 (1.85%)
Mucosal infection †	4/54 (7.41%)
Papulopustular rash †	1/54 (1.85%)
Paronychia †	1/54 (1.85%)
Periorbital infection †	1/54 (1.85%)
Pharyngitis †	2/54 (3.70%)
Rash pustular †	2/54 (3.70%)
Sepsis †	3/54 (5.56%)
Sinusitis †	2/54 (3.70%)
Skin infection †	4/54 (7.41%)
Upper respiratory infection †	7/54 (12.96%)
Urinary tract infection †	3/54 (5.56%)
Vaginal infection †	1/54 (1.85%)
Injury, poisoning and procedural complications
Bruising †	1/54 (1.85%)
Fall †	2/54 (3.70%)
Investigations
Alanine aminotransferase increased †	6/54 (11.11%)
Alkaline phosphatase increased †	15/54 (27.78%)
Aspartate aminotransferase increased †	13/54 (24.07%)
Blood bilirubin increased †	2/54 (3.70%)
Cholesterol high †	1/54 (1.85%)
Creatinine increased †	6/54 (11.11%)
Electrocardiogram QT corrected interval prolonged †	1/54 (1.85%)
INR increased †	1/54 (1.85%)
Investigations-Other †	4/54 (7.41%)
Lymphocyte count decreased †	10/54 (18.52%)
Neutrophil count decreased †	11/54 (20.37%)
Platelet count decreased †	9/54 (16.67%)
Weight gain †	3/54 (5.56%)
Weight loss †	6/54 (11.11%)
White blood cell decreased †	10/54 (18.52%)
Metabolism and nutrition disorders
Acidosis †	1/54 (1.85%)
Anorexia †	16/54 (29.63%)
Dehydration †	11/54 (20.37%)
Hypercalcemia †	1/54 (1.85%)
Hyperglycemia †	7/54 (12.96%)
Hyperkalemia †	4/54 (7.41%)
Hypermagnesemia †	1/54 (1.85%)
Hypernatremia †	1/54 (1.85%)
Hypoalbuminemia †	24/54 (44.44%)
Hypocalcemia †	13/54 (24.07%)
Hypoglycemia †	1/54 (1.85%)
Hypokalemia †	8/54 (14.81%)
Hypomagnesemia †	8/54 (14.81%)
Hyponatremia †	18/54 (33.33%)
Hypophosphatemia †	1/54 (1.85%)
Metabolism and nutrition disorders - Other, specify †	2/54 (3.70%)
Musculoskeletal and connective tissue disorders
Arthralgia †	5/54 (9.26%)
Arthritis †	1/54 (1.85%)
Back pain †	7/54 (12.96%)
Bone pain †	3/54 (5.56%)
Chest wall pain †	1/54 (1.85%)
Flank pain †	1/54 (1.85%)
Generalized muscle weakness †	7/54 (12.96%)
Muscle weakness lower limb †	1/54 (1.85%)
Musculoskeletal and connective tiss disorder - Other †	5/54 (9.26%)
Myalgia †	6/54 (11.11%)
Pain in extremity †	3/54 (5.56%)
Nervous system disorders
Ataxia †	1/54 (1.85%)
Depressed level of consciousness †	1/54 (1.85%)
Dizziness †	6/54 (11.11%)
Dysgeusia †	8/54 (14.81%)
Dysphasia †	1/54 (1.85%)
Encephalopathy †	1/54 (1.85%)
Headache †	5/54 (9.26%)
Lethargy †	1/54 (1.85%)
Nervous system disorders-Other †	1/54 (1.85%)
Peripheral sensory neuropathy †	7/54 (12.96%)
Tremor †	1/54 (1.85%)
Psychiatric disorders
Anxiety †	2/54 (3.70%)
Confusion †	5/54 (9.26%)
Depression †	2/54 (3.70%)
Hallucinations †	1/54 (1.85%)
Insomnia †	5/54 (9.26%)
Renal and urinary disorders
Acute kidney injury †	1/54 (1.85%)
Proteinuria †	2/54 (3.70%)
Renal and urinary disorders-Other †	2/54 (3.70%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis †	1/54 (1.85%)
Bronchopulmonary hemorrhage †	1/54 (1.85%)
Cough †	13/54 (24.07%)
Dyspnea †	18/54 (33.33%)
Epistaxis †	11/54 (20.37%)
Hiccups †	1/54 (1.85%)
Hoarseness †	2/54 (3.70%)
Hypoxia †	2/54 (3.70%)
Nasal congestion †	7/54 (12.96%)
Pleural effusion †	2/54 (3.70%)
Pleuritic pain †	1/54 (1.85%)
Pneumonitis †	5/54 (9.26%)
Postnasal drip †	1/54 (1.85%)
Productive cough †	5/54 (9.26%)
Pulmonary hypertension †	1/54 (1.85%)
Resp, thoracic and mediastinal disorders - Other †	2/54 (3.70%)
Respiratory failure †	1/54 (1.85%)
Sore throat †	4/54 (7.41%)
Voice alteration †	2/54 (3.70%)
Wheezing †	2/54 (3.70%)
Skin and subcutaneous tissue disorders
Alopecia †	11/54 (20.37%)
Dry skin †	17/54 (31.48%)
Erythema multiforme †	2/54 (3.70%)
Nail discoloration †	4/54 (7.41%)
Nail loss †	4/54 (7.41%)
Palmar-plantar erythrodysesthesia syndrome †	1/54 (1.85%)
Periorbital edema †	6/54 (11.11%)
Pruritus †	8/54 (14.81%)
Rash acneiform †	17/54 (31.48%)
Rash maculo-papular †	20/54 (37.04%)
Scalp pain †	1/54 (1.85%)
Skin and subcutaneous tissue disorders - Other †	9/54 (16.67%)
Skin ulceration †	1/54 (1.85%)
Vascular disorders
Flushing †	2/54 (3.70%)
Hot flashes †	1/54 (1.85%)
Hypertension †	15/54 (27.78%)
Hypotension †	8/54 (14.81%)
Thromboembolic event †	3/54 (5.56%)
Vascular disorders-Other †	1/54 (1.85%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Lung Committee Statistician
• Organization: SWOG Statistics and Data Management Center
• Phone: 2066674623
• EMail: jmiao@fredhutch.org

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02642042
• Other Study ID Numbers: NCI-2015-02250; NCI-2015-02250 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S1507; S1507 ( Other Identifier: SWOG ); S1507 ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• First Submitted: December 29, 2015
• First Posted: December 30, 2015
• Results First Submitted: December 1, 2020
• Results First Posted: February 2, 2021
• Last Update Posted: May 3, 2023