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A Study of MM-121 Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00994123
Recruitment Status : Completed
First Posted : October 14, 2009
Results First Posted : August 22, 2016
Last Update Posted : August 22, 2016
Sponsor:
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: MM-121
Drug: Erlotinib
Enrollment 162
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1: MM-121 + Erlotinib Phase 2: MM-121 + Erlotinib Phase 2: Erlotinib
Hide Arm/Group Description Escalating doses of MM-121 and erlotinib

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

Period Title: Overall Study
Started 33 85 44
Completed 33 85 44
Not Completed 0 0 0
Arm/Group Title Phase 1: MM-121 + Erlotinib Phase 2: MM-121 + Erlotinib Phase 2: Erlotinib Total
Hide Arm/Group Description Escalating doses of MM-121 + Erlotinib in patients with NSCLC

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

Total of all reporting groups
Overall Number of Baseline Participants 33 85 44 162
Hide Baseline Analysis Population Description
Ph 1: Patients with NSCLC Ph 2:Patients whose tumors are wild-type for EGFR and who have not received prior EGFR TKI targeted therapy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 85 participants 44 participants 162 participants
63.5  (10.12) 62.9  (10.74) 63.9  (10.16) 63.2  (10.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 85 participants 44 participants 162 participants
Female
17
  51.5%
35
  41.2%
17
  38.6%
69
  42.6%
Male
16
  48.5%
50
  58.8%
27
  61.4%
93
  57.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 85 participants 44 participants 162 participants
Hispanic or Latino
2
   6.1%
3
   3.5%
1
   2.3%
6
   3.7%
Not Hispanic or Latino
31
  93.9%
82
  96.5%
43
  97.7%
156
  96.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 85 participants 44 participants 162 participants
American Indian or Alaska Native
0
   0.0%
1
   1.2%
0
   0.0%
1
   0.6%
Asian
0
   0.0%
7
   8.2%
6
  13.6%
13
   8.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   6.1%
3
   3.5%
2
   4.5%
7
   4.3%
White
31
  93.9%
74
  87.1%
36
  81.8%
141
  87.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Phase 1: To Determine the Recommended Phase 2 Dose of the MM-121 + Erlotinib Combination Based Upon Either the Maximum Tolerated Dose (MTD) or the Maximum Feasible Dose of the Combination in Patients With NSCLC.
Hide Description To establish the safety of escalating doses of MM-121 in combination with erlotinib in order to determine the recommended phase 2 dose of the combination for the second part of the study. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
Time Frame From date of first dose to 30 days after termination, the longest 175 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7
Hide Arm/Group Description:
MM-121 6 mk/kg (Q2W IV) and 100 mg erlotinib (daily PO)
6 mg/kg MM-121 Q2W + 150 mg erlotinib (daily PO)
MM-121 12 mg/kg (Q2W IV) + 100 mg erlotinib (daily PO)
MM-121 12 mg/kg (Q2W IV) + 150 mg erlotinib (PO daily)
MM-121 20 mg/kg (weekly IV) + erlotinib 100 mg (PO daily)
MM-121 20 mg/kg (Q2W IV) + erlotinib 100 mg (PO daily)
MM-121 20 mg/kg (Q3W IV) + erlotinib 100 mg (PO daily)
Overall Number of Participants Analyzed 1 3 6 3 6 8 6
Measure Type: Number
Unit of Measure: participants reporting DLTs
0 0 1 1 1 0 0
2.Primary Outcome
Title Phase 1: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Hide Description

Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs.

The determined MTD was used as the recommended Phase 2 dose.

Time Frame From date of first dose to 30 days after termination, the longest 175 weeks
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Hide Analysis Population Description
All participants treated in the Phase 1 dose-escalation portion of the study
Arm/Group Title Phase 1: All Participants
Hide Arm/Group Description:
All participants in the dose escalation portion of the Phase 1
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: dose level of MTD
NA [1] 
[1]
Maximum tolerated dose was not reached. Recommended Phase 2 Dose (MM-121 mg/kg IV Q2W + erlotinib 100 mg PO daily) was selected based on Investigator agreement on safety profile and PK parameters.
3.Primary Outcome
Title Phase 2: Progression-free Survival of the MM-121 + Erlotinib Combination
Hide Description This was a time-to-event measure using Progression-Free Survival (PFS) comparing MM-121 + erlotinib vs.erlotinib alone. Progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression free survival was defined as the number of weeks from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD).
Time Frame Time from first dose to date of progression, with a median of 8.1 weeks
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title MM-121 + Erlotinib Erlotinib
Hide Arm/Group Description:

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

Overall Number of Participants Analyzed 85 44
Median (95% Confidence Interval)
Unit of Measure: weeks
8.1
(7.7 to 8.9)
7.7
(7.1 to 8.1)
4.Post-Hoc Outcome
Title To Explore the Utility of an EGFR Family Receptor-ligand (Heregulin, HRG) as a Predictor of Response to MM-121 and /or Erlotinib in Formalin Fixed (FFPE) Tumor Samples
Hide Description Tumor tissue samples were obtained from patients prior to enrollment. Samples were analyzed using RNA-ISH for the expression of the biomarker, heregulin. Progression-free survival was assessed using RECIST v 1.1 to determine whether patients whose tumors express HRG have a lower PFS than those whose tumors do not express HRG, and to assess whether the addition of MM-121 to erlotinib can increase PFS in HRG-high patients.
Time Frame Time from first dose to date of progression, with a median of 8.1 weeks
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Hide Analysis Population Description
Patients with available tissue for heregulin testing
Arm/Group Title HRG High: MM-121 + Erlotinib HRG High: Erlotinib HRG Low: Erlotinib HRG Low: MM-121 + Erlotinib
Hide Arm/Group Description:

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

Overall Number of Participants Analyzed 23 13 12 20
Median (95% Confidence Interval)
Unit of Measure: months PFS
1.9
(1.7 to 4)
1.7 [1] 
(1 to NA)
2.3 [1] 
(1.7 to NA)
1.6
(1.4 to 1.9)
[1]
Upper bound was not evaluable due to too few events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HRG High: MM-121 + Erlotinib, HRG High: Erlotinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.16 to 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HRG Low: Erlotinib, HRG Low: MM-121 + Erlotinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.15
Confidence Interval (2-Sided) 95%
0.97 to 4.76
Estimation Comments [Not Specified]
Time Frame AEs were collected from a patient's first dose until 30 days after treatment termination. SAEs were collected from time of informed consent until 30 days after termination. If related, events could be reported at any time after termination.
Adverse Event Reporting Description All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination.
 
Arm/Group Title Ph 2: MM-121 + Erlotinib Ph 2: Erlotinib Ph 1: MM-121 + Erlotinib
Hide Arm/Group Description

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.

EGFR wild-type, EGFR-TKI naive patients randomized to receive:

daily 150 mg erlotinib p.o. alone

Escalating Doses of MM-121 + erlotinib
All-Cause Mortality
Ph 2: MM-121 + Erlotinib Ph 2: Erlotinib Ph 1: MM-121 + Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ph 2: MM-121 + Erlotinib Ph 2: Erlotinib Ph 1: MM-121 + Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/85 (47.06%)   18/44 (40.91%)   16/33 (48.48%) 
Blood and lymphatic system disorders       
Anemia * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Cardiac disorders       
Cardiac Arrest * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Cardiopulmonary Failure * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Intracardiac Thrombus * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Tachycardia * 1  0/85 (0.00%)  1/44 (2.27%)  1/33 (3.03%) 
Ventricular Fibrillation * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Cardiac Tamponade * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Gastrointestinal disorders       
Diarrhea * 1  2/85 (2.35%)  1/44 (2.27%)  1/33 (3.03%) 
Gastritis * 1  2/85 (2.35%)  0/44 (0.00%)  0/33 (0.00%) 
Abdominal Pain * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Abdominal Pain Upper * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Ileus * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Small Intestinal Obstruction * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Vomiting * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Stomatitis * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
General disorders       
Disease Progression * 1  14/85 (16.47%)  3/44 (6.82%)  1/33 (3.03%) 
Chest Pain * 1  1/85 (1.18%)  1/44 (2.27%)  0/33 (0.00%) 
Asthenia * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Gait Disturbance * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Fatigue * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Pain * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Infections and infestations       
Pneumonia * 1  4/85 (4.71%)  4/44 (9.09%)  1/33 (3.03%) 
Bronchopneumonia * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Klebsiella Infection * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Localized Infection * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Scrotal Infection * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Sepsis * 1  1/85 (1.18%)  0/44 (0.00%)  1/33 (3.03%) 
Septic Shock * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Upper Respiratory Tract Infection * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Urinary Tract Infection * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Bronchitis * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Injury, poisoning and procedural complications       
Pelvic Fracture * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Investigations       
General Physical Condition Abnormal * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
International Normalized Ratio Increased * 1  1/85 (1.18%)  0/44 (0.00%)  1/33 (3.03%) 
Electrocardiogram QT prolonged * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Metabolism and nutrition disorders       
Dehydration * 1  1/85 (1.18%)  1/44 (2.27%)  2/33 (6.06%) 
Failure to thrive * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Back Pain * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Bone Pain * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Musculoskeletal chest pain * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Groin Pain * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasm Progression * 1  1/85 (1.18%)  1/44 (2.27%)  0/33 (0.00%) 
Colon Cancer * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Lung Neoplasm Malignant * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Metastases to Central Nervous System * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Pituitary Tumor Benign * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Non-small cell lung cancer * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Pericardial effusion * 1  0/85 (0.00%)  0/44 (0.00%)  0/33 (0.00%) 
Nervous system disorders       
Cerebral Infarction * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Cerebrovascular accident * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Complex Partial Seizures * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Dizziness * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Spinal Cord Compression * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Psychiatric disorders       
Mental Status Changes * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Renal and urinary disorders       
Renal Failure Acute * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Reproductive system and breast disorders       
Pelvic Pain * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea * 1  4/85 (4.71%)  3/44 (6.82%)  0/33 (0.00%) 
Pulmonary Embolism * 1  3/85 (3.53%)  1/44 (2.27%)  3/33 (9.09%) 
Pleural Effusion * 1  2/85 (2.35%)  1/44 (2.27%)  0/33 (0.00%) 
Aspiration * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Chronic Obstructive Pulmonary Disease * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Hypoxia * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Pneumonitis * 1  0/85 (0.00%)  1/44 (2.27%)  0/33 (0.00%) 
Respiratory Failure * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Acute Respiratory Failure * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Acute Respiratory Distress Syndrome * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Skin and subcutaneous tissue disorders       
Dermatitis Acneform * 1  0/85 (0.00%)  1/44 (2.27%)  1/33 (3.03%) 
Vascular disorders       
Hemorrhage * 1  1/85 (1.18%)  0/44 (0.00%)  0/33 (0.00%) 
Deep Vein Thrombosis * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Orthostatic hypotension * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
Venous Occlusion * 1  0/85 (0.00%)  0/44 (0.00%)  1/33 (3.03%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ph 2: MM-121 + Erlotinib Ph 2: Erlotinib Ph 1: MM-121 + Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/85 (100.00%)   44/44 (100.00%)   33/33 (100.00%) 
Blood and lymphatic system disorders       
Anemia * 1  9/85 (10.59%)  4/44 (9.09%)  7/33 (21.21%) 
Thrombocytopenia * 1  2/85 (2.35%)  0/44 (0.00%)  2/33 (6.06%) 
Cardiac disorders       
TACHYCARDIA * 1  1/85 (1.18%)  1/44 (2.27%)  3/33 (9.09%) 
CARDIAC TAMPONADE * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
PERICARDIAL EFFUSION * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
SUPRAVENTRICULAR TACHYCARDIA * 1  2/85 (2.35%)  0/44 (0.00%)  2/33 (6.06%) 
Eye disorders       
CONJUNCTIVITIS * 1  3/85 (3.53%)  0/44 (0.00%)  4/33 (12.12%) 
EYE PAIN * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
EYE PRURITUS * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
LACRIMATION INCREASED * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Gastrointestinal disorders       
Diarrhea * 1  59/85 (69.41%)  27/44 (61.36%)  27/33 (81.82%) 
Nausea * 1  29/85 (34.12%)  14/44 (31.82%)  9/33 (27.27%) 
Vomiting * 1  19/85 (22.35%)  11/44 (25.00%)  8/33 (24.24%) 
Stomatitis * 1  20/85 (23.53%)  5/44 (11.36%)  7/33 (21.21%) 
Constipation * 1  10/85 (11.76%)  7/44 (15.91%)  6/33 (18.18%) 
Abdominal Pain * 1  5/85 (5.88%)  1/44 (2.27%)  3/33 (9.09%) 
Dysphagia * 1  3/85 (3.53%)  0/44 (0.00%)  3/33 (9.09%) 
Gastroesophageal reflux disease * 1  2/85 (2.35%)  1/44 (2.27%)  4/33 (12.12%) 
Abdominal Distension * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Abdominal Pain Upper * 1  4/85 (4.71%)  2/44 (4.55%)  2/33 (6.06%) 
CHEILITIS * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
DRY MOUTH * 1  3/85 (3.53%)  0/44 (0.00%)  2/33 (6.06%) 
ORAL DISCOMFORT * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
General disorders       
Fatigue * 1  31/85 (36.47%)  13/44 (29.55%)  21/33 (63.64%) 
Disease Progression * 1  14/85 (16.47%)  3/44 (6.82%)  1/33 (3.03%) 
Asthenia * 1  7/85 (8.24%)  6/44 (13.64%)  3/33 (9.09%) 
Pyrexia * 1  6/85 (7.06%)  7/44 (15.91%)  1/33 (3.03%) 
Mucosal Inflammation * 1  9/85 (10.59%)  3/44 (6.82%)  7/33 (21.21%) 
Peripheral Edema * 1  4/85 (4.71%)  3/44 (6.82%)  6/33 (18.18%) 
Early Satiety * 1  1/85 (1.18%)  0/44 (0.00%)  7/33 (21.21%) 
Pain * 1  0/85 (0.00%)  0/44 (0.00%)  4/33 (12.12%) 
Chills * 1  4/85 (4.71%)  1/44 (2.27%)  2/33 (6.06%) 
Hepatobiliary disorders       
hyperbilirubinemia * 1  3/85 (3.53%)  1/44 (2.27%)  2/33 (6.06%) 
Infections and infestations       
Pneumonia * 1  6/85 (7.06%)  6/44 (13.64%)  2/33 (6.06%) 
Paronychia * 1  9/85 (10.59%)  2/44 (4.55%)  7/33 (21.21%) 
Urinary Tract Infection * 1  4/85 (4.71%)  4/44 (9.09%)  9/33 (27.27%) 
Nasopharyngitis * 1  3/85 (3.53%)  3/44 (6.82%)  0/33 (0.00%) 
CANDIDIASIS * 1  0/85 (0.00%)  0/44 (0.00%)  3/33 (9.09%) 
FUNGAL SKIN INFECTION * 1  2/85 (2.35%)  1/44 (2.27%)  3/33 (9.09%) 
UPPER RESPIRATORY TRACT * 1  4/85 (4.71%)  1/44 (2.27%)  3/33 (9.09%) 
VULVOVAGINAL MYCOTIC INFECTION * 1  0/85 (0.00%)  0/44 (0.00%)  3/33 (9.09%) 
NAIL INFECTION * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Oral Herpes * 1  3/85 (3.53%)  0/44 (0.00%)  2/33 (6.06%) 
Sepsis * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Injury, poisoning and procedural complications       
Excoriation * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Skin laceration * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Investigations       
Weight Decreased * 1  27/85 (31.76%)  11/44 (25.00%)  9/33 (27.27%) 
Blood Creatinine Increased * 1  7/85 (8.24%)  3/44 (6.82%)  2/33 (6.06%) 
Aspartate Aminotransferase Increased * 1  6/85 (7.06%)  2/44 (4.55%)  2/33 (6.06%) 
Alanine Aminotransferase Increased * 1  6/85 (7.06%)  1/44 (2.27%)  1/33 (3.03%) 
Blood Magnesium Decreased * 1  6/85 (7.06%)  0/44 (0.00%)  0/33 (0.00%) 
Blook Alkaline Phosphatase Increased * 1  5/85 (5.88%)  0/44 (0.00%)  3/33 (9.09%) 
Electrocardiogram QT prolonged * 1  0/85 (0.00%)  0/44 (0.00%)  3/33 (9.09%) 
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Breath Sounds Abnormal * 1  1/85 (1.18%)  1/44 (2.27%)  2/33 (6.06%) 
Metabolism and nutrition disorders       
Decreased Appetite * 1  37/85 (43.53%)  16/44 (36.36%)  11/33 (33.33%) 
Hypokalemia * 1  14/85 (16.47%)  3/44 (6.82%)  8/33 (24.24%) 
Dehydration * 1  7/85 (8.24%)  5/44 (11.36%)  11/33 (33.33%) 
Hypomagnesemia * 1  6/85 (7.06%)  3/44 (6.82%)  8/33 (24.24%) 
Hyperglycemia * 1  5/85 (5.88%)  1/44 (2.27%)  0/33 (0.00%) 
Hyponatremia * 1  3/85 (3.53%)  1/44 (2.27%)  3/33 (9.09%) 
HYPOPHOSPHATAEMIA * 1  0/85 (0.00%)  1/44 (2.27%)  3/33 (9.09%) 
HYPERKALAEMIA * 1  0/85 (0.00%)  2/44 (4.55%)  2/33 (6.06%) 
HYPOCALCAEMIA * 1  1/85 (1.18%)  1/44 (2.27%)  2/33 (6.06%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  9/85 (10.59%)  4/44 (9.09%)  6/33 (18.18%) 
Musculoskeletal pain * 1  8/85 (9.41%)  3/44 (6.82%)  3/33 (9.09%) 
Musculoskeletal chest pain * 1  6/85 (7.06%)  3/44 (6.82%)  1/33 (3.03%) 
Pain in Extremity * 1  3/85 (3.53%)  1/44 (2.27%)  6/33 (18.18%) 
Back Pain * 1  15/85 (17.65%)  4/44 (9.09%)  5/33 (15.15%) 
Muscle Spasms * 1  1/85 (1.18%)  1/44 (2.27%)  4/33 (12.12%) 
Muscle weakness * 1  2/85 (2.35%)  1/44 (2.27%)  4/33 (12.12%) 
Flank Pain * 1  1/85 (1.18%)  1/44 (2.27%)  2/33 (6.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
METASTASES TO CENTRAL NERVOUS SYSTEM * 1  2/85 (2.35%)  0/44 (0.00%)  2/33 (6.06%) 
Nervous system disorders       
Dizziness * 1  11/85 (12.94%)  8/44 (18.18%)  4/33 (12.12%) 
Dysgeusia * 1  14/85 (16.47%)  1/44 (2.27%)  6/33 (18.18%) 
Headache * 1  7/85 (8.24%)  3/44 (6.82%)  3/33 (9.09%) 
NEUROPATHY PERIPHERAL * 1  2/85 (2.35%)  1/44 (2.27%)  3/33 (9.09%) 
AMNESIA * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
PARAESTHESIA * 1  3/85 (3.53%)  2/44 (4.55%)  2/33 (6.06%) 
SYNCOPE * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Psychiatric disorders       
Anxiety * 1  8/85 (9.41%)  2/44 (4.55%)  4/33 (12.12%) 
Depression * 1  5/85 (5.88%)  3/44 (6.82%)  2/33 (6.06%) 
Insomnia * 1  5/85 (5.88%)  1/44 (2.27%)  12/33 (36.36%) 
Confusional State * 1  1/85 (1.18%)  3/44 (6.82%)  0/33 (0.00%) 
Agitation * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Renal and urinary disorders       
Dysuria * 1  2/85 (2.35%)  0/44 (0.00%)  5/33 (15.15%) 
HAEMATURIA * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
NOCTURIA * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
PROTEINURIA * 1  1/85 (1.18%)  0/44 (0.00%)  2/33 (6.06%) 
Reproductive system and breast disorders       
Breast Pain * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea * 1  22/85 (25.88%)  9/44 (20.45%)  6/33 (18.18%) 
Cough * 1  16/85 (18.82%)  6/44 (13.64%)  12/33 (36.36%) 
Dysphonia * 1  10/85 (11.76%)  1/44 (2.27%)  4/33 (12.12%) 
Epistaxis * 1  10/85 (11.76%)  1/44 (2.27%)  6/33 (18.18%) 
Productive Cough * 1  6/85 (7.06%)  2/44 (4.55%)  1/33 (3.03%) 
Dyspnea Exertional * 1  2/85 (2.35%)  0/44 (0.00%)  6/33 (18.18%) 
Oropharyngeal Pain * 1  4/85 (4.71%)  1/44 (2.27%)  4/33 (12.12%) 
WHEEZING * 1  2/85 (2.35%)  0/44 (0.00%)  4/33 (12.12%) 
HAEMOPTYSIS * 1  4/85 (4.71%)  0/44 (0.00%)  3/33 (9.09%) 
PULMONARY EMBOLISM * 1  3/85 (3.53%)  2/44 (4.55%)  3/33 (9.09%) 
RHINORRHOEA * 1  4/85 (4.71%)  1/44 (2.27%)  3/33 (9.09%) 
RHONCHI * 1  0/85 (0.00%)  1/44 (2.27%)  3/33 (9.09%) 
SINUS DISORDER * 1  0/85 (0.00%)  0/44 (0.00%)  3/33 (9.09%) 
HYPOXIA * 1  3/85 (3.53%)  0/44 (0.00%)  2/33 (6.06%) 
Nasal Inflammation * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Skin and subcutaneous tissue disorders       
Rash * 1  46/85 (54.12%)  21/44 (47.73%)  15/33 (45.45%) 
Dry Skin * 1  28/85 (32.94%)  11/44 (25.00%)  11/33 (33.33%) 
Dermatitis Acneform * 1  14/85 (16.47%)  12/44 (27.27%)  12/33 (36.36%) 
Pruritis * 1  10/85 (11.76%)  10/44 (22.73%)  0/33 (0.00%) 
Rash Maculo-papular * 1  4/85 (4.71%)  4/44 (9.09%)  3/33 (9.09%) 
Palmar-Plantar Erythrodysasthesia Syndrome * 1  4/85 (4.71%)  3/44 (6.82%)  3/33 (9.09%) 
Skin Disorder * 1  5/85 (5.88%)  2/44 (4.55%)  1/33 (3.03%) 
Skin Exfoliation * 1  3/85 (3.53%)  3/44 (6.82%)  1/33 (3.03%) 
Alopecia * 1  5/85 (5.88%)  0/44 (0.00%)  3/33 (9.09%) 
Skin Fissures * 1  0/85 (0.00%)  3/44 (6.82%)  1/33 (3.03%) 
ONYCHOCLASIS * 1  3/85 (3.53%)  0/44 (0.00%)  4/33 (12.12%) 
Skin Ulcer * 1  0/85 (0.00%)  0/44 (0.00%)  2/33 (6.06%) 
Vascular disorders       
HYPERTENSION * 1  1/85 (1.18%)  1/44 (2.27%)  2/33 (6.06%) 
ORTHOSTATIC HYPOTENSION * 1  0/85 (0.00%)  1/44 (2.27%)  2/33 (6.06%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.1)
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: Clinical Trial Manager
Organization: Merrimack Pharmaceuticals
Phone: 617-441-1000
Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00994123     History of Changes
Other Study ID Numbers: MM-121-01-101
First Submitted: October 13, 2009
First Posted: October 14, 2009
Results First Submitted: February 14, 2016
Results First Posted: August 22, 2016
Last Update Posted: August 22, 2016