Trial Outcomes & Findings for Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy (NCT NCT00965250)

NCT ID: NCT00965250

Last Updated: 2016-12-23

Results Overview

Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug.
• Results posted on: 2016-12-23

Participant Flow

The thymic carcinoma cohort was closed after enrolment of 12 participants because of lack of activity.

Participant milestones

Measure	Thymoma Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Overall Study STARTED	37	12
Overall Study COMPLETED	37	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy

Baseline characteristics by cohort

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants	11 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Gender Female	18 Participants n=5 Participants	5 Participants n=7 Participants	23 Participants n=5 Participants
Gender Male	19 Participants n=5 Participants	7 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized White, non-Hispanic	25 participants n=5 Participants	5 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized White, Hispanic	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	1 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants	12 participants n=7 Participants	49 participants n=5 Participants
Median age	52 years n=5 Participants	55 years n=7 Participants	52 years n=5 Participants
Metastatic Sites Intrathoracic sites only	18 participants n=5 Participants	0 participants n=7 Participants	18 participants n=5 Participants
Metastatic Sites Extrathoracic sites(w/without intrathoracic sites	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants
Histological Analysis (WHO classification) AB	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Histological Analysis (WHO classification) B1	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Histological Analysis (WHO classification) B2	15 participants n=5 Participants	0 participants n=7 Participants	15 participants n=5 Participants
Histological Analysis (WHO classification) B2/B3	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Histological Analysis (WHO classification) B3	9 participants n=5 Participants	0 participants n=7 Participants	9 participants n=5 Participants
Histological Analysis (WHO classification) C	0 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants
Histological Analysis (WHO classification) Not otherwise specified	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Paraneoplastic Syndromes Myastenia gravis	9 participants n=5 Participants	0 participants n=7 Participants	9 participants n=5 Participants
Paraneoplastic Syndromes Shulman's syndrome	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Paraneoplastic Syndromes Pure red-cell aplasia	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Paraneoplastic Syndromes Crohn's disease	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Paraneoplastic Syndromes Ulcerative colitis	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Paraneoplastic Syndromes Mucocutaneous candidiasis	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Previous systemic treatment (number of regimens)	3 regimens n=5 Participants	2 regimens n=7 Participants	2 regimens n=5 Participants
Previous systemic treatment (six or more regimens)	10 participants n=5 Participants	2 participants n=7 Participants	12 participants n=5 Participants
Previous chemotherapy One line	12 participants n=5 Participants	7 participants n=7 Participants	19 participants n=5 Participants
Previous chemotherapy Two lines	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants
Previous chemotherapy Three or more lines	17 participants n=5 Participants	3 participants n=7 Participants	20 participants n=5 Participants
Previous platinum treatment	37 participants n=5 Participants	12 participants n=7 Participants	49 participants n=5 Participants
Previous anthracycline	27 participants n=5 Participants	5 participants n=7 Participants	32 participants n=5 Participants
Investigational drugs	17 participants n=5 Participants	4 participants n=7 Participants	21 participants n=5 Participants
Previous radiotherapy	23 participants n=5 Participants	4 participants n=7 Participants	27 participants n=5 Participants
Previous surgery Radical	28 participants n=5 Participants	2 participants n=7 Participants	30 participants n=5 Participants
Previous surgery Debulking	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Previous surgery Biopsy	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Normal Activity	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Symptoms, but ambulatory	29 participants n=5 Participants	8 participants n=7 Participants	37 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 - In bed <50% of the time	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug.

Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. Complete Response	0 Participants	0 Participants
Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. Partial Response	5 Participants	0 Participants
Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. Stable Disease	28 Participants	5 Participants
Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. Progressive Disease	4 Participants	7 Participants

SECONDARY outcome

Timeframe: 81 months and 17 days

Population: Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Outcome measures

Measure	Thymoma n=49 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Number of Participants With Adverse Events	49 Participants	—

SECONDARY outcome

Timeframe: 39 months

Percentage of participants who respond to treatment was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Percentage of Participants Who Respond to Treatment	14 percentage of participants Interval 5.0 to 29.0	0 percentage of participants Interval 0.0 to 26.0

SECONDARY outcome

Timeframe: 39 months

Disease control rate is defined as objective response plus stable disease.

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Disease Control Rate (DCR)	89 percentage of participants Interval 75.0 to 97.0	42 percentage of participants Interval 15.0 to 72.0

SECONDARY outcome

Timeframe: 39 months

Time between the first day of treatment to the day of disease progression.

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Time to Progression	9.9 Months Interval 7.3 to 12.8	1.7 Months Interval 0.9 to 2.7

SECONDARY outcome

Timeframe: 39 months

Time from treatment start date until date of death or date last known alive.

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Overall Survival	27.5 Months Interval 15.0 to NA represents an undefined upper limit of the confidence interval because there were insufficient events (deaths) for it to be determined.	8.4 Months Interval 4.7 to 12.8

SECONDARY outcome

Timeframe: 6 weeks

A cycle is defined as 21 days or 6 weeks of therapy.

Outcome measures

Measure	Thymoma n=37 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.	Thymic Carcinoma n=12 Participants Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
Median Number of Cycles of Therapy	13 Cycles Interval 2.0 to 46.0	2.5 Cycles Interval 1.0 to 8.0

SECONDARY outcome

Timeframe: 6 weeks after initiation of treatment

Population: We did radiological assessment ourselves, and an independent radiological assessment was not undertaken for assessment of response or progression.

Participants with scans that showed neither sufficient shrinkage to qualify as an objective response nor sufficient increase to qualify as disease progression, taking as reference the smallest cumulative longest dimension since start of treatment, to have stable disease.

Outcome measures

Outcome data not reported

Adverse Events

IMC-A12 Monotherapy in Patients

Serious events: 29 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	IMC-A12 Monotherapy in Patients n=49 participants at risk Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks.
General disorders Death NOS	44.9% 22/49 • Number of events 22 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Mucositis Oral	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Abdominal pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Bone pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Chest wall pain	2.0% 1/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Rectal pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Chills	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Seizure	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders CPK increased	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Bronchial infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Diarrhea	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Enterocolitis infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Fever	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hyperglycemia	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Lung infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Cardiac disorders Myocardial infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Myositis	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mailgnant and unspecified	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Soft tissue infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Vascular disorders Thromboembolic event	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.

Other adverse events

Measure	IMC-A12 Monotherapy in Patients n=49 participants at risk Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks.
Gastrointestinal disorders Abdominal distention	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Abdominal pain	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Activated partial thromboplastin time prolonged	14.3% 7/49 • Number of events 12 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Cardiac disorders Acute coronary syndrome	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Alanine aminotransferase increased	46.9% 23/49 • Number of events 60 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Alkaline phosphatase increased	34.7% 17/49 • Number of events 31 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Immune system disorders Allergic reaction	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Immune system disorders Allergic rhinitis	14.3% 7/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Alopecia	14.3% 7/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Anemia	71.4% 35/49 • Number of events 105 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Cough	32.7% 16/49 • Number of events 31 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Diarrhea	18.4% 9/49 • Number of events 22 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Dizziness	10.2% 5/49 • Number of events 8 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Dry eye	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Dry mouth	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Dry skin	12.2% 6/49 • Number of events 6 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Dysgeusia	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Dyspnea	26.5% 13/49 • Number of events 20 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify (patient reports of diminished hearing)	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Edema: limbs	2.0% 1/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.2% 5/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Reproductive system and breast disorders Erectile dysfunction	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Eye disorders - Other, specify (Aur; lost vision R eye)	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Eye pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Fatigue	36.7% 18/49 • Number of events 44 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Fever	6.1% 3/49 • Number of events 5 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Flank pain	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Flashing lights	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Floaters	8.2% 4/49 • Number of events 5 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Flu like symptoms	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Gastroesophageal reflux disease	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	8.2% 4/49 • Number of events 5 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Headache	12.2% 6/49 • Number of events 11 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Ear and labyrinth disorders Hearing impaired	6.1% 3/49 • Number of events 4 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Hemorroids	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Hiccups	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Hoarseness	8.2% 4/49 • Number of events 9 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypercalcemia	28.6% 14/49 • Number of events 26 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hyperglycemia	75.5% 37/49 • Number of events 182 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hyperkalemia	20.4% 10/49 • Number of events 24 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypermagnesemia	18.4% 9/49 • Number of events 20 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypernatremia	20.4% 10/49 • Number of events 17 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hyperuricemia	44.9% 22/49 • Number of events 57 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypoalbuminemia	79.6% 39/49 • Number of events 110 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypocalcemia	14.3% 7/49 • Number of events 20 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypoglycemia	14.3% 7/49 • Number of events 10 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypokalemia	12.2% 6/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypophosphatemia	10.2% 5/49 • Number of events 11 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hypomagnesemia	40.8% 20/49 • Number of events 59 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Cardiac disorders Hypotension	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders INR increased	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Infections and infestations - Other, specify (Opportunistic; thrush)	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Immune system disorders Infusion related reaction	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Insomnia	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Investigations Investigations-Other, specify (Bicarbonate, serum-low)	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Kidney infection	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Lipase increased	12.2% 6/49 • Number of events 22 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	2.0% 1/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Lymphocyte count decreased	40.8% 20/49 • Number of events 63 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders lymphocyte count increased	16.3% 8/49 • Number of events 14 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Mucosal infection	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Mucositis oral	18.4% 9/49 • Number of events 18 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder-Other, specify	26.5% 13/49 • Number of events 15 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Myalgia	10.2% 5/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Nail discoloration	2.0% 1/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Nail loss	10.2% 5/49 • Number of events 5 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Nausea	34.7% 17/49 • Number of events 27 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Neck pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mailgnant and unspecified	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Neutrophil count decreased	16.3% 8/49 • Number of events 29 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Oral pain	4.1% 2/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Pain	6.1% 3/49 • Number of events 6 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Cardiac disorders Palpitations	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Peripheral sensory neuropathy	16.3% 8/49 • Number of events 12 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Platelet count decreased	32.7% 16/49 • Number of events 45 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Immune system disorders Postnasal drip	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Presyncope	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Rash acneiform	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Rash maculo-papular	12.2% 6/49 • Number of events 8 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Rectal pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Renal and urinary disorders Renal and urinary disorders - Other, specify (urinary hesitancy)	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Serum amylase increased	16.3% 8/49 • Number of events 18 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Cardiac disorders Sinus bradycardia	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Sinusitis	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	8.2% 4/49 • Number of events 4 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Skin ulceration	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Ear and labyrinth disorders Tinnitus	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Tooth infection	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Tremor	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Tumor pain	16.3% 8/49 • Number of events 11 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	16.3% 8/49 • Number of events 9 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Renal and urinary disorders Urinary tract infection	8.2% 4/49 • Number of events 4 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Vertigo	10.2% 5/49 • Number of events 8 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Voice alteration	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Vomiting	22.4% 11/49 • Number of events 18 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
General disorders Weight loss	12.2% 6/49 • Number of events 14 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders White blood cell decreased	22.4% 11/49 • Number of events 40 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Hyponatremia	61.2% 30/49 • Number of events 78 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Dyspepsia	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Creatinine increased	34.7% 17/49 • Number of events 68 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Constipation	14.3% 7/49 • Number of events 16 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Anorexia	40.8% 20/49 • Number of events 29 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Aspartate aminotransferase increased	46.9% 23/49 • Number of events 59 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Ataxia	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Back pain	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Bladder infection	6.1% 3/49 • Number of events 3 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Blood and lymphatic system disorders Bronchopulmonary hemorrhage	6.1% 3/49 • Number of events 4 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders CPK increased	18.4% 9/49 • Number of events 17 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Gastrointestinal disorders Bloating	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Blood bilirubin increased	16.3% 8/49 • Number of events 26 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Blurred vision	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Infections and infestations Bronchial infection	12.2% 6/49 • Number of events 7 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Chest wall pain	12.2% 6/49 • Number of events 11 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Cognitive disturbance	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Nervous system disorders Confusion	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Eye disorders Conjunctivitis	4.1% 2/49 • Number of events 2 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Facial muscle weakness	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Metabolism and nutrition disorders Glucose intolerance	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Pain in extremity	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Pruritis	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Respiratory, thoracic and mediastinal disorders Sore throat	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Renal and urinary disorders Urinary frequency	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Musculoskeletal and connective tissue disorders Bone pain	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.
Skin and subcutaneous tissue disorders Skin hypopigmentation	2.0% 1/49 • Number of events 1 Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups.

Additional Information

Dr. Arun Rajan

National Cancer Institute, National Institutes of Health

Phone: 301-594-5322

Email: rajana@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place