Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT01964924
• Recruitment Status: Completed
• First Posted: October 17, 2013
• Results First Posted: September 20, 2019
• Last Update Posted: September 20, 2019
• Sponsor: National Cancer Institute (NCI)
• Collaborator: GlaxoSmithKline
• 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: Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma
• Interventions: Drug: Akt Inhibitor GSK2141795; Other: Laboratory Biomarker Analysis; Drug: Trametinib
• Enrollment: 37

Participant Flow

Recruitment Details
Pre-assignment Details	Patients on Part 1: trametinib monotherapy until progression and then will continue on to Part 2: trametinib combined with GSK2141795.

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression in Part 1 continue to Part 2.	PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Period Title: Trametinib Monotherapy
Started	37	0
Completed	18	0
Not Completed	19	0
Reason Not Completed
Progression	19	0
Period Title: Trametinib + GSK2141
Started [1]	0	19 [2]
Completed	0	19
Not Completed	0	0
[1] Participants who completed Part 1 were not eligible for Part 2; [2] Progressed in Part 1 and therefore initiated combination treatment in Part 2

Baseline Characteristics

Arm/Group Title		Treatment (Trametinib, Akt Inhibitor GSK2141795)
Arm/Group Description		PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Baseline Participants		37
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	37 participants
		57; (35 to 71)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	Female	37 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	37 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 10.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 5.4%
	White	31 83.8%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	37 participants
		37

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR), Defined as the Proportion of Patients Who Have Had a Partial Response (PR) or Complete Response (CR) (RECIST 1.1 Based) Within the First 6 Months After Initiation of Therapy With Trametinib
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795)
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37
Measure Type: Count of Participants; Unit of Measure: Participants
	2 5.4%

2. Secondary Outcome

Title	Clinical Benefit Rate (CBR = CR+PR+Stable Disease [SD])
Description	The clinical benefit rate (CR+PR+SD) will be reported for patients after Part 1 and after Part 2.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37	19
Measure Type: Count of Participants; Unit of Measure: Participants
	8 21.6%	6 31.6%

3. Secondary Outcome

Title	Duration of Objective Response
Description	Summary statistics of duration of response for patients with objective response
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	8	6
Mean (Standard Deviation); Unit of Measure: days of response
	162.75 (149.26)	87.00 (62.86)

4. Secondary Outcome

Title	Incidence of Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment
Description	Incidence of adverse events for patients that are classified as either possibly, probably, or definitely related to study treatment graded by National Cancer Institute (NCI) CTCAE v4.0
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	37	19
Measure Type: Number; Unit of Measure: number of adverse events
	227	204

5. Secondary Outcome

Title	Incidence of Severe (Grade 3+) Adverse Events or Toxicities Graded Per NCI CTCAE Version 4.0
Description	NCI CommonTerminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for grading incidence of toxicities (grade 3+).
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	37	19
Measure Type: Number; Unit of Measure: number of adverse events
	68	29

6. Secondary Outcome

Title	Overall Survival
Description	The Kaplan-Meier method will be used to estimate overall survival distribution.
Time Frame	Start date of the treatment to the date of the event (i.e., death) or the date of last follow-up to evaluate that event, assessed up to 52 weeks

Outcome Measure Data

Analysis Population Description

overall survival analyzed for all patients regardless of (part 1 only) or (part 1 and 2) participation

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795)
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37
Median (95% Confidence Interval); Unit of Measure: weeks
	43.143; (33.0 to 99.286)

7. Secondary Outcome

Title	Progression-free Survival
Description	The Kaplan-Meier method will be used to estimate progression-free survival distribution.
Time Frame	The duration of time from start of treatment to time of progression or death, whichever comes first, assessed up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.	PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37	19
Median (95% Confidence Interval); Unit of Measure: weeks
	7.71; (4.43 to 8.29)	7.86; (5.86 to 13.86)

8. Secondary Outcome

Title	Proportion of Patients Who go Off Treatment Due to Adverse Reactions
Description	The proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was captured. These tolerability measures were assessed within each of the treatment parts independently. All patients who have received at least one dose of any of the therapeutic agents was evaluable for toxicity and tolerability.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795)	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37	19
Measure Type: Count of Participants; Unit of Measure: Participants
	4 10.8%	0 0.0%

9. Secondary Outcome

Title	Proportion of Patients Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial
Description	[Not Specified]
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

The proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was in Part I

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795)	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37	0
Measure Type: Count of Participants; Unit of Measure: Participants
	2 5.4%	0

10. Secondary Outcome

Title	Tolerability of the Regimen Defined as the Number of Patients Who Required Dose Modifications and/or Dose Delays
Description	[Not Specified]
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795)	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description:	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO	PART 2: Patients who experience disease progression in Part 1 continue to Part 2. Patients receive trametinib and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Akt Inhibitor GSK2141795: Given PO Laboratory Biomarker Analysis: Correlative studies Trametinib: Given PO
Overall Number of Participants Analyzed	37	19
Measure Type: Count of Participants; Unit of Measure: Participants
	35 94.6%	0 0.0%

11. Other Pre-specified Outcome

Title	Predictive Value of PTEN and Other Biomarkers on Patient Outcome (Survival, ORR, and CBR)
Description	[Not Specified]
Time Frame	At time of disease progression, assessed up to 52 weeks

Outcome Measure Data Not Reported

12. Other Pre-specified Outcome

Title	Protein Intensity Fold-change Ratios Assessed by Reverse Phase Protein Assay Intensity Values
Description	Ratios between tumors sampled prior to initiating trametinib single agent treatment and at time of progression (TOP) on either single agent trametinib or the combination (TOP/pre-treat ratio), will be calculated. These ratios will be median-centered and clustered using Cluster 2.0 software. Student's t-test for differences between average protein intensity ratios at these intervals will be calculated using Microsoft Excel by grouping all the ratios for individual clusters.
Time Frame	Up to 52 weeks

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Up to 1 year patients will be evaluated for toxicities from the time of their first treatment until they are off study.
Adverse Event Reporting Description	Adverse Event grading was done using NCI CTCAE version 4.0
Arm/Group Title	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:		Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
Arm/Group Description	PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2.		PART 2: Patients receive trametinib as in Part 1 and also receive Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:		Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
	Affected / at Risk (%)		Affected / at Risk (%)
Total	13/37 (35.14%)		12/19 (63.16%)
Serious Adverse Events
	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:		Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/37 (81.08%)		15/19 (78.95%)
Blood and lymphatic system disorders
Anemia † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Leukocytosis † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Cardiac disorders
Cardiac arrest † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Gastrointestinal disorders
Diarrhea † 1	0/37 (0.00%)	0	2/19 (10.53%)	2
Dysphagia † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Enterocolitis † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Vomiting † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
General disorders
Death NOS † 1	1/37 (2.70%)	1	4/19 (21.05%)	4
Edema face † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Edema limbs † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Fever † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
General disorders and administration site conditions - Other, specify † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Infections and infestations
Infections and infestations - Other, specify † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Sepsis † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Skin infection † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Investigations
Alkaline phosphatase increased † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Hypoalbuminemia † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Hypocalcemia † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Hypoglycemia † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1	8/37 (21.62%)	8	3/19 (15.79%)	3
Nervous system disorders
Hypoglossal nerve disorder † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Syncope † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Renal and urinary disorders
Renal and urinary disorders - Other, specify † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Reproductive system and breast disorders
Breast pain † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Pleural effusion † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Pneumonitis † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Vascular disorders
Hypertension † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
Thromboembolic event † 1	1/37 (2.70%)	1	0/19 (0.00%)	0
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 1:		Treatment (Trametinib, Akt Inhibitor GSK2141795) PART 2:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/37 (100.00%)		19/19 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	7/37 (18.92%)	7	8/19 (42.11%)	8
Cardiac disorders
Heart failure † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Left ventricular systolic dysfunction † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Sinus tachycardia † 1	3/37 (8.11%)	3	0/19 (0.00%)	0
Ventricular tachycardia † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Endocrine disorders
Hyperthyroidism † 1	2/37 (5.41%)	2	1/19 (5.26%)	1
Hypothyroidism † 1	1/37 (2.70%)	1	2/19 (10.53%)	2
Eye disorders
Blurred vision † 1	1/37 (2.70%)	1	2/19 (10.53%)	2
Gastrointestinal disorders
Abdominal distension † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Abdominal pain † 1	3/37 (8.11%)	3	0/19 (0.00%)	0
Colitis † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Constipation † 1	5/37 (13.51%)	5	0/19 (0.00%)	0
Diarrhea † 1	11/37 (29.73%)	11	16/19 (84.21%)	16
Dry mouth † 1	4/37 (10.81%)	4	1/19 (5.26%)	1
Dyspepsia † 1	4/37 (10.81%)	4	0/19 (0.00%)	0
Dysphagia † 1	2/37 (5.41%)	2	5/19 (26.32%)	5
Esophageal pain † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Gastroesophageal reflux disease † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Gastrointestinal disorders - Other, specify † 1	2/37 (5.41%)	2	2/19 (10.53%)	2
Mucositis oral † 1	4/37 (10.81%)	4	12/19 (63.16%)	13
Nausea † 1	12/37 (32.43%)	12	5/19 (26.32%)	6
Vomiting † 1	6/37 (16.22%)	6	3/19 (15.79%)	3
General disorders
Edema face † 1	4/37 (10.81%)	4	1/19 (5.26%)	1
Edema limbs † 1	11/37 (29.73%)	11	4/19 (21.05%)	4
Edema trunk † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Facial pain † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Fatigue † 1	11/37 (29.73%)	11	6/19 (31.58%)	6
Fever † 1	3/37 (8.11%)	3	0/19 (0.00%)	0
Flu like symptoms † 1	2/37 (5.41%)	2	1/19 (5.26%)	1
Localized edema † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Neck edema † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Non-cardiac chest pain † 1	2/37 (5.41%)	2	3/19 (15.79%)	3
Pain † 1	4/37 (10.81%)	4	2/19 (10.53%)	2
Infections and infestations
Infections and infestations - Other, specify † 1	1/37 (2.70%)	1	3/19 (15.79%)	4
Paronychia † 1	1/37 (2.70%)	1	2/19 (10.53%)	2
Skin infection † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Urinary tract infection † 1	2/37 (5.41%)	2	1/19 (5.26%)	1
Injury, poisoning and procedural complications
Bruising † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Fall † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Vascular access complication † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Investigations
Alanine aminotransferase increased † 1	7/37 (18.92%)	7	2/19 (10.53%)	2
Alkaline phosphatase increased † 1	6/37 (16.22%)	6	3/19 (15.79%)	3
Aspartate aminotransferase increased † 1	13/37 (35.14%)	13	4/19 (21.05%)	4
Creatinine increased † 1	4/37 (10.81%)	4	3/19 (15.79%)	3
Ejection fraction decreased † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Electrocardiogram QT corrected interval prolonged † 1	0/37 (0.00%)	0	2/19 (10.53%)	2
INR increased † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Investigations - Other, specify † 1	0/37 (0.00%)	0	2/19 (10.53%)	3
Lymphocyte count decreased † 1	6/37 (16.22%)	6	4/19 (21.05%)	4
Neutrophil count decreased † 1	1/37 (2.70%)	1	2/19 (10.53%)	3
Platelet count decreased † 1	7/37 (18.92%)	7	3/19 (15.79%)	3
Weight gain † 1	3/37 (8.11%)	3	1/19 (5.26%)	1
Weight loss † 1	1/37 (2.70%)	1	3/19 (15.79%)	4
White blood cell decreased † 1	5/37 (13.51%)	5	6/19 (31.58%)	7
Metabolism and nutrition disorders
Anorexia † 1	5/37 (13.51%)	5	2/19 (10.53%)	2
Dehydration † 1	1/37 (2.70%)	1	5/19 (26.32%)	5
Hypercalcemia † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Hyperglycemia † 1	7/37 (18.92%)	7	6/19 (31.58%)	8
Hypoalbuminemia † 1	9/37 (24.32%)	9	7/19 (36.84%)	8
Hypocalcemia † 1	3/37 (8.11%)	3	4/19 (21.05%)	5
Hypoglycemia † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Hypokalemia † 1	3/37 (8.11%)	3	2/19 (10.53%)	6
Hypomagnesemia † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Hyponatremia † 1	3/37 (8.11%)	3	1/19 (5.26%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Back pain † 1	3/37 (8.11%)	3	4/19 (21.05%)	4
Flank pain † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Generalized muscle weakness † 1	3/37 (8.11%)	3	2/19 (10.53%)	2
Neck pain † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Pain in extremity † 1	4/37 (10.81%)	4	2/19 (10.53%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps-Other † 1	1/37 (2.70%)	1	2/19 (10.53%)	2
Tumor pain † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Nervous system disorders
Dizziness † 1	3/37 (8.11%)	3	1/19 (5.26%)	1
Dysgeusia † 1	0/37 (0.00%)	0	2/19 (10.53%)	2
Dysphasia † 1	0/37 (0.00%)	0	2/19 (10.53%)	2
Headache † 1	4/37 (10.81%)	4	0/19 (0.00%)	0
Movements involuntary † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Peripheral motor neuropathy † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Peripheral sensory neuropathy † 1	5/37 (13.51%)	5	4/19 (21.05%)	4
Presyncope † 1	0/37 (0.00%)	0	1/19 (5.26%)	2
Psychiatric disorders
Anxiety † 1	4/37 (10.81%)	4	0/19 (0.00%)	0
Depression † 1	4/37 (10.81%)	4	0/19 (0.00%)	0
Insomnia † 1	2/37 (5.41%)	2	2/19 (10.53%)	2
Renal and urinary disorders
Hematuria † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Urinary frequency † 1	2/37 (5.41%)	2	2/19 (10.53%)	2
Reproductive system and breast disorders
Breast pain † 1	1/37 (2.70%)	1	1/19 (5.26%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/37 (8.11%)	3	2/19 (10.53%)	2
Dyspnea † 1	9/37 (24.32%)	9	8/19 (42.11%)	8
Epistaxis † 1	1/37 (2.70%)	1	3/19 (15.79%)	3
Hoarseness † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Hypoxia † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Nasal congestion † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Pleural effusion † 1	5/37 (13.51%)	5	0/19 (0.00%)	0
Pneumonitis † 1	0/37 (0.00%)	0	3/19 (15.79%)	3
Sore throat † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Voice alteration † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	3/37 (8.11%)	3	1/19 (5.26%)	1
Dry skin † 1	5/37 (13.51%)	5	4/19 (21.05%)	4
Nail ridging † 1	2/37 (5.41%)	2	0/19 (0.00%)	0
Palmar-plantar erythrodysesthesia syndrome † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Pruritus † 1	6/37 (16.22%)	6	3/19 (15.79%)	5
Rash acneiform † 1	10/37 (27.03%)	10	3/19 (15.79%)	5
Rash maculo-papular † 1	6/37 (16.22%)	6	3/19 (15.79%)	3
Skin and subcutaneous tissue disorders - Other, specify † 1	4/37 (10.81%)	4	3/19 (15.79%)	3
Vascular disorders
Hypertension † 1	5/37 (13.51%)	5	7/19 (36.84%)	9
Hypotension † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
Lymphedema † 1	5/37 (13.51%)	5	2/19 (10.53%)	2
Thromboembolic event † 1	0/37 (0.00%)	0	1/19 (5.26%)	1
1 Term from vocabulary, CTCAE (4.0); † 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: Bhuvaneswari Ramaswamy
• Organization: The Ohio State University Comprehensive Cancer Center
• Phone: 614-293-8858
• EMail: Bhuvaneswari.Ramaswamy@osumc.edu

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01964924
• Other Study ID Numbers: NCI-2013-01895; NCI-2013-01895 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2013C0069; OSU 13117; 9455 ( Other Identifier: Ohio State University Comprehensive Cancer Center ); 9455 ( Other Identifier: CTEP ); N01CM00070 ( U.S. NIH Grant/Contract ); N01CM00100 ( U.S. NIH Grant/Contract ); P30CA016058 ( U.S. NIH Grant/Contract ); UM1CA186712 ( U.S. NIH Grant/Contract ); UM1CA186716 ( U.S. NIH Grant/Contract )
• First Submitted: October 15, 2013
• First Posted: October 17, 2013
• Results First Submitted: December 17, 2018
• Results First Posted: September 20, 2019
• Last Update Posted: September 20, 2019