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Trial record 1 of 3 for:    erlotinib, Hydroxychloroquine
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Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations

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ClinicalTrials.gov Identifier: NCT00977470
Recruitment Status : Active, not recruiting
First Posted : September 15, 2009
Results First Posted : June 6, 2017
Last Update Posted : February 5, 2019
Sponsor:
Collaborators:
Stanford University
Yale University
University of Maryland
Genentech, Inc.
Information provided by (Responsible Party):
Lecia V. Sequist, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Erlotinib
Drug: Hydroxychloroquine
Enrollment 76
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Period Title: Overall Study
Started 38 38
Completed 0 0
Not Completed 38 38
Reason Not Completed
Lack of Efficacy             32             30
Physician Decision             2             0
Adverse Event             1             2
Protocol Violation             1             0
Withdrawal by Subject             0             2
Death             0             2
clinical decline             0             1
prolonged recovery post-surgery             0             1
Still on-study             2             0
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine Total
Hide Arm/Group Description Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Total of all reporting groups
Overall Number of Baseline Participants 38 38 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 38 participants 38 participants 76 participants
63
(43 to 84)
65
(37 to 82)
64
(37 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 38 participants 76 participants
Female
24
  63.2%
23
  60.5%
47
  61.8%
Male
14
  36.8%
15
  39.5%
29
  38.2%
Smoking History  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 38 participants 76 participants
Never smoked
28
  73.7%
20
  52.6%
48
  63.2%
<= 10 pack years
4
  10.5%
8
  21.1%
12
  15.8%
> 10 pack years/current
6
  15.8%
10
  26.3%
16
  21.1%
Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 38 participants 76 participants
Adenocarcinoma
33
  86.8%
31
  81.6%
64
  84.2%
Non-small cell lung cancer, Not Otherwise Specifie
5
  13.2%
7
  18.4%
12
  15.8%
Brain metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 38 participants 76 participants
11
  28.9%
16
  42.1%
27
  35.5%
Prior chemotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 38 participants 76 participants
9
  23.7%
13
  34.2%
22
  28.9%
1.Primary Outcome
Title Median Progression Free Survival
Hide Description A measure of progression-free survival in patients with advanced non small-cell lung cancer (NSCLC) and EGFR mutations treated with erlotinib as compared with patients treated with erlotinib plus hydroxychloroquine (HCQ). Disease progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, as seen on CT scan, or the appearance of one or more new lesions on CT scan.
Time Frame From start of treatment until report of disease progression, assessed up to 10 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 38 38
Median (Full Range)
Unit of Measure: months
10.8
(9.0 to 13.6)
10.8
(7.0 to 14.6)
2.Primary Outcome
Title Nine-month Progression-free Survival Rate
Hide Description This trial can detect a difference in proportions alive without progression at 9 months from 50% in the erlotinib arm to 77% in the erlotinib plus hydroxychloroquine (HCQ) arm, using an alpha of 0.15 and power of 85%, using the two-sided Likelihood Ratio test. Progression is defined as at least a 20% increase in the size of existing lesions or the appearance of one or more new lesions.
Time Frame Nine months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 38 38
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
71
(53 to 83)
52
(35 to 67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erlotinib, Erlotinib and Hydroxychloroquine
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments All enrolled patients will be included in the intent-to-treat efficacy analyses. Based on historical patients with EGFR mutations treated with gefitinib, we expect median progression-free survival on the erlotinib-alone arm to be approximately 9 months. This trial can detect a difference in proportions alive without progression at 9 months from 50% in the erlotinib arm to 77% in the erlotinib plus HCQ arm, using an alpha of 0.15 and power of 85%, using the two-sided Likelihood Ratio test.
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Treatment Related Toxicity, > 10% Frequency, Any Grade
Hide Description To evaluate the safety of treatment with erlotinib with and without hydroxychloroquine (HCQ). All participants receiving study treatment were evaluated for safety. Parameters included laboratory tests, hematological abnormalities, physical exam findings and spontaneous reports of adverse events reported by participants. Toxicities were evaluated and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = fatal.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 38 38
Measure Type: Count of Participants
Unit of Measure: Participants
Diarrhea
30
  78.9%
32
  84.2%
Rash
17
  44.7%
21
  55.3%
Fatigue
15
  39.5%
21
  55.3%
Grade 3 Fatigue
1
   2.6%
7
  18.4%
Nausea
11
  28.9%
21
  55.3%
Anorexia
9
  23.7%
11
  28.9%
Taste changes
9
  23.7%
9
  23.7%
Grade 3 Taste changes
0
   0.0%
1
   2.6%
Alopecia
5
  13.2%
7
  18.4%
Weight loss
5
  13.2%
7
  18.4%
Ocular toxicity
6
  15.8%
4
  10.5%
Grade 4 or 5 events
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.
Hide Description

Response is assessed via spiral CT scan, done at baseline and after every 2 cycles of study treatment. Standard RECIST (Response Evaluation Criteria in Solid Tumors) was used. Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the size of target lesions, as compared to baseline; Progressive Disease (PD) = at least at 20% increase in the size of target lesions, or the appearance of one or more new lesions; Stable Disease (SD) = neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

Response rate = CR + PR. Disease control rate = CR + PR + SD

Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
1 participant in each arm (2 participants total) did not have any scans done after baseline and therefore response could not be assessed.
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 37 37
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
1
   2.7%
2
   5.4%
Partial Response
23
  62.2%
19
  51.4%
Stable Disease
10
  27.0%
10
  27.0%
Progressive Disease
3
   8.1%
6
  16.2%
Response Rate
24
  64.9%
21
  56.8%
Disease Control Rate
34
  91.9%
31
  83.8%
5.Secondary Outcome
Title Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ
Hide Description [Not Specified]
Time Frame Until death
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Circulating Tumor Cell Quantification
Hide Description Serial circulating tumor cell (CTC) analyses will be performed on peripheral blood and correlated with disease response.
Time Frame Until disease progression (median of 10.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to technical reasons, this assay was not ready and therefore circulating tumor cell analysis was not done.
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Other Pre-specified Outcome
Title EGFR Mutational Status
Hide Description Correlation of molecular and genetic tumor characteristics with disease response. Genomic DNA will be extracted from tumor tissue and direct sequencing analysis will be performed to identify additional mutations.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Tumor tissue analysis was not performed for this correlative outcome.
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Other Pre-specified Outcome
Title Percent of Participants in Which FMISO-PET ([18F]-Fluoromisonidazole-positron Emission Tomography) is Able to Detect and Quantify Changes in Tumor Hypoxia After Erlotinib.
Hide Description [18F]-FMISO-PET/CT was performed on a 64-slice PET/CT scanner and tracer uptake was assessed using SUV (standardized uptake value), normalizing the radioactivity measured in tissue by the injected dose and the body weight of the patient. Mean and maximum SUV and threshold volume of FMISO uptake were measured to quantify the extent of hypoxia in the primary tumor. Imaging was performed before and after initiation of therapy with erlotinib.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only 2 participants were enrolled in this pilot companion study
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description:
Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Overall Number of Participants Analyzed 2 0
Measure Type: Count of Participants
Unit of Measure: Participants
2
 100.0%
0
Time Frame 1 year
Adverse Event Reporting Description Adverse events were collected via physical exam, eye exam and laboratory test. Additionally, participants were questioned at each study visit regarding other events not collected by the above methods.
 
Arm/Group Title Erlotinib Erlotinib and Hydroxychloroquine
Hide Arm/Group Description Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

All-Cause Mortality
Erlotinib Erlotinib and Hydroxychloroquine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Erlotinib Erlotinib and Hydroxychloroquine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/38 (10.53%)      2/38 (5.26%)    
General disorders     
Constitutional disorders - other  1 [1]  1/38 (2.63%)  0/38 (0.00%) 
Death NOS  1  0/38 (0.00%)  1/38 (2.63%) 
Infections and infestations     
Infection, nos  1  0/38 (0.00%)  1/38 (2.63%) 
Pneumonia  1  1/38 (2.63%)  0/38 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/38 (2.63%)  0/38 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumothorax  1  0/38 (0.00%)  1/38 (2.63%) 
Respiratory - other  1 [2]  1/38 (2.63%)  0/38 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin - pain  1  1/38 (2.63%)  0/38 (0.00%) 
Vascular disorders     
Pulmonary embolism  1  1/38 (2.63%)  0/38 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Failure to Thrive
[2]
Pneumomediastinum
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Erlotinib Erlotinib and Hydroxychloroquine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/38 (100.00%)      38/38 (100.00%)    
Blood and lymphatic system disorders     
Leukocytes  1  1/38 (2.63%)  1 2/38 (5.26%)  4
Lymphopenia  1  3/38 (7.89%)  4 2/38 (5.26%)  6
Neutrophils  1  1/38 (2.63%)  3 1/38 (2.63%)  1
Platelets  1  4/38 (10.53%)  4 0/38 (0.00%)  0
Hematologic-other  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Lymph node, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Cardiac disorders     
Palpitations  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Atrial fibrillation  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Sinus tachycardia  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Arrhythmia-other  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Cardiac-other  1  1/38 (2.63%)  1 2/38 (5.26%)  2
Ear and labyrinth disorders     
Tinnitus  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Hearing-other  1  1/38 (2.63%)  1 2/38 (5.26%)  3
External ear, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Endocrine disorders     
Hypoparathyroidism  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Hyopthyroidism  1  3/38 (7.89%)  3 0/38 (0.00%)  0
Endocrine-other  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Eye disorders     
Cataract  1  2/38 (5.26%)  2 1/38 (2.63%)  1
Dry eye syndrome  1  3/38 (7.89%)  3 5/38 (13.16%)  5
Eyelid dysfunction  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Glaucoma  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Double vision  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Retinopathy  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Vision-blurred  1  7/38 (18.42%)  7 2/38 (5.26%)  2
Vision-flashing lights/floaters  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Ocular-other  1  8/38 (21.05%)  9 7/38 (18.42%)  8
Gastrointestinal disorders     
Constipation  1  12/38 (31.58%)  13 11/38 (28.95%)  12
Diarrhea w/o prior colostomy  1  33/38 (86.84%)  43 32/38 (84.21%)  44
Distention/bloating, abdominal  1  4/38 (10.53%)  4 3/38 (7.89%)  3
Dry mouth  1  1/38 (2.63%)  1 5/38 (13.16%)  7
Dysphagia  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Flatulence  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Dyspepsia  1  5/38 (13.16%)  7 7/38 (18.42%)  7
Hemorrhoids  1  3/38 (7.89%)  3 0/38 (0.00%)  0
Ileus  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Muco/stomatitis by exam, anus  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Muco/stomatitis by exam, oral cavity  1  1/38 (2.63%)  2 1/38 (2.63%)  1
Muco/stomatitis (symptom) oral cavity  1  2/38 (5.26%)  2 1/38 (2.63%)  1
Muco/stomatitis (symptom) pharynx  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Nausea  1  18/38 (47.37%)  22 23/38 (60.53%)  38
Taste disturbance  1  10/38 (26.32%)  11 10/38 (26.32%)  14
Vomiting  1  7/38 (18.42%)  8 9/38 (23.68%)  10
GI-other  1  1/38 (2.63%)  1 7/38 (18.42%)  9
Anus, hemorrhage  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Abdomen, pain  1  6/38 (15.79%)  7 2/38 (5.26%)  2
Oral cavity, pain  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Oral gums, pain  1  3/38 (7.89%)  3 0/38 (0.00%)  0
Stomach, pain  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Throat/pharynx/larynx, pain  1  2/38 (5.26%)  2 0/38 (0.00%)  0
General disorders     
Fatigue  1  25/38 (65.79%)  32 27/38 (71.05%)  44
Fever w/o neutropenia  1  1/38 (2.63%)  1 2/38 (5.26%)  2
Rigors/chills  1  4/38 (10.53%)  4 2/38 (5.26%)  3
Sweating  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Constitutional, other  1  5/38 (13.16%)  5 1/38 (2.63%)  1
Growth and Development, Other  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Hemorrhage-other  1  2/38 (5.26%)  2 1/38 (2.63%)  1
Edema limb  1  6/38 (15.79%)  7 2/38 (5.26%)  2
Head/headache  1  11/38 (28.95%)  12 7/38 (18.42%)  7
Pain NOS  1  2/38 (5.26%)  3 3/38 (7.89%)  4
Pain-other  1  8/38 (21.05%)  8 8/38 (21.05%)  10
Flu-like syndrome  1  3/38 (7.89%)  3 0/38 (0.00%)  0
Immune system disorders     
Allergic reaction  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Allergy-other  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Infections and infestations     
Infection w/ gr3-4 neut, ungual (nails)  1  1/38 (2.63%)  3 0/38 (0.00%)  0
Infection Gr0-2 neut, bladder  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection Gr0-2 neut, bronchus  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection Gr0-2 neut, lung  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection Gr0-2 neut, skin  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Infection Gr0-2 neut, ungual  1  3/38 (7.89%)  5 3/38 (7.89%)  3
Infection Gr0-2 neut, upper airway  1  4/38 (10.53%)  4 5/38 (13.16%)  5
Infection Gr0-2 neut, urinary tract  1  4/38 (10.53%)  5 4/38 (10.53%)  5
Infection Gr0-2 neut, vagina  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Infection Gr0-2 neut, wound  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Infection w/ unk ANC eye NOS  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Infection w/ unk ANC joint  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Infection w/ unk ANC lung  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Infection w/ unk ANC oral cavity/gums  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection w/ unk ANC skin (cellulitis)  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection w/ unk ANC ungual (nails)  1  1/38 (2.63%)  1 1/38 (2.63%)  2
Infection w/ unk ANC upper airway NOS  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Infection w/ unk ANC urinary tract NOS  1  3/38 (7.89%)  3 0/38 (0.00%)  0
Infection-other  1  4/38 (10.53%)  5 3/38 (7.89%)  3
Injury, poisoning and procedural complications     
Bruising  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Fracture  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Investigations     
Hemoglobin  1  4/38 (10.53%)  6 1/38 (2.63%)  3
Weight loss  1  7/38 (18.42%)  8 8/38 (21.05%)  9
INR  1  1/38 (2.63%)  1 0/38 (0.00%)  0
ADH secretion abnormality (eg SIADH)  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia  1  13/38 (34.21%)  15 15/38 (39.47%)  23
Dehydration  1  2/38 (5.26%)  3 5/38 (13.16%)  6
Hypoalbuminemia  1  2/38 (5.26%)  2 1/38 (2.63%)  2
Alkaline phosphatase  1  3/38 (7.89%)  3 3/38 (7.89%)  4
ALT, SGPT  1  7/38 (18.42%)  8 5/38 (13.16%)  5
AST, SGOT  1  5/38 (13.16%)  6 6/38 (15.79%)  7
Bilirubin  1  4/38 (10.53%)  6 2/38 (5.26%)  2
Hypercalcemia  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Hypocalcemia  1  0/38 (0.00%)  0 3/38 (7.89%)  5
Hypercholesterolemia  1  2/38 (5.26%)  2 3/38 (7.89%)  3
Creatinine  1  3/38 (7.89%)  4 4/38 (10.53%)  4
Hyperglycemia  1  3/38 (7.89%)  4 1/38 (2.63%)  3
Hypoglycemia  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Hypomagnesemia  1  3/38 (7.89%)  4 1/38 (2.63%)  1
Hypophosphatemia  1  2/38 (5.26%)  2 2/38 (5.26%)  3
Hyperkalemia  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Hypokalemia  1  6/38 (15.79%)  9 2/38 (5.26%)  2
Hyponatremia  1  2/38 (5.26%)  2 6/38 (15.79%)  6
Metabolic/Laboratory-other  1  1/38 (2.63%)  1 2/38 (5.26%)  3
Musculoskeletal and connective tissue disorders     
Arthritis  1  3/38 (7.89%)  3 4/38 (10.53%)  4
Joint-function  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Osteoporosis  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Musculoskeletal/soft tissue-other  1  6/38 (15.79%)  8 2/38 (5.26%)  2
Back, pain  1  10/38 (26.32%)  13 7/38 (18.42%)  7
Bone, pain  1  3/38 (7.89%)  4 1/38 (2.63%)  1
Breast, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Buttock, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Chest wall, pain  1  2/38 (5.26%)  3 1/38 (2.63%)  1
Chest/thoracic pain NOS  1  3/38 (7.89%)  4 5/38 (13.16%)  7
Extremity-limb, pain  1  9/38 (23.68%)  11 1/38 (2.63%)  1
Face, pain  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Joint, pain  1  7/38 (18.42%)  7 3/38 (7.89%)  4
Lip, pain  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Muscle, pain  1  1/38 (2.63%)  1 2/38 (5.26%)  3
Neck, pain  1  1/38 (2.63%)  2 1/38 (2.63%)  1
Pelvic, pain  1  2/38 (5.26%)  3 1/38 (2.63%)  1
Pleura, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Secondary malignancy  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Breast volume/hypoplasia  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Nervous system disorders     
Nonneuropathic lower extr muscle weak  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Nonneuropathic generalized weakness  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Cognitive disturbance  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Dizziness  1  11/38 (28.95%)  12 7/38 (18.42%)  7
Memory impairment  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Neuropathy-motor  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Neuropathy-sensory  1  5/38 (13.16%)  6 2/38 (5.26%)  2
Seizure  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Neurologic-other  1  9/38 (23.68%)  9 5/38 (13.16%)  6
Psychiatric disorders     
Insomnia  1  3/38 (7.89%)  3 10/38 (26.32%)  10
Confusion  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Anxiety  1  11/38 (28.95%)  11 5/38 (13.16%)  5
Depression  1  6/38 (15.79%)  6 4/38 (10.53%)  5
Renal and urinary disorders     
Urinary frequency/urgency  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Renal/GU-other  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Reproductive system and breast disorders     
Vagina, hemorrhage  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Vagina, pain  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Irregular menses  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Sexual/Reproductive function-Other  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  3/38 (7.89%)  3 2/38 (5.26%)  2
Lung, hemorrhage  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Nose, hemorrhage  1  6/38 (15.79%)  7 2/38 (5.26%)  2
Esophagus, pain  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Bronchospasm, wheezing  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Cough  1  23/38 (60.53%)  24 16/38 (42.11%)  16
Dyspnea  1  16/38 (42.11%)  21 12/38 (31.58%)  14
Hiccoughs  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Nasal cavity/paranasal sinus reaction  1  1/38 (2.63%)  1 1/38 (2.63%)  1
Pleural effusion (non-malignant)  1  0/38 (0.00%)  0 2/38 (5.26%)  2
Pneumothorax  1  0/38 (0.00%)  0 2/38 (5.26%)  2
Voice changes/dysarthria  1  2/38 (5.26%)  2 5/38 (13.16%)  6
Pulmonary/Upper Respiratory-other  1  6/38 (15.79%)  6 2/38 (5.26%)  2
Skin and subcutaneous tissue disorders     
Chelitis  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Dry skin  1  12/38 (31.58%)  18 12/38 (31.58%)  13
Alopecia  1  6/38 (15.79%)  7 10/38 (26.32%)  10
Hyperpigmentation  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Hypopigmentation  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Nail changes  1  3/38 (7.89%)  3 3/38 (7.89%)  3
Pruritus/itching  1  4/38 (10.53%)  4 3/38 (7.89%)  3
Rash/desquamation  1  20/38 (52.63%)  31 13/38 (34.21%)  18
Rash: acne/acneiform  1  18/38 (47.37%)  25 21/38 (55.26%)  28
Hand-foot reaction  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Skin breakdown/decubitus ulcer  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Ulceration  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Skin-other  1  20/38 (52.63%)  25 8/38 (21.05%)  10
Petechiae  1  0/38 (0.00%)  0 1/38 (2.63%)  1
Skin, pain  1  4/38 (10.53%)  4 1/38 (2.63%)  2
Vascular disorders     
Hypertension  1  10/38 (26.32%)  10 6/38 (15.79%)  6
Hypotension  1  2/38 (5.26%)  3 1/38 (2.63%)  1
Flushing  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Thrombosis/thrombus/embolism  1  2/38 (5.26%)  2 0/38 (0.00%)  0
Vascular-Other (Specify)  1  1/38 (2.63%)  1 0/38 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Maria Kempner
Organization: Mass General Hospital Cancer Center
Phone: 508-533-4132
Responsible Party: Lecia V. Sequist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00977470     History of Changes
Other Study ID Numbers: 09-097
OSI4620s ( Other Identifier: OSI )
First Submitted: September 11, 2009
First Posted: September 15, 2009
Results First Submitted: March 22, 2017
Results First Posted: June 6, 2017
Last Update Posted: February 5, 2019