Trial Outcomes & Findings for Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery (NCT NCT00521001)

Last Updated: 2017-08-14

Results Overview

The primary endpoint of this trial is the 9 week PFS rate. A patient is a success if they are progression free at their cycle 2 evaluation (approximately 9 weeks post registration). All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 9-week PFS rate (evaluable patients). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. If some patients are lost to follow up prior to their cycle 2 evaluation, the Kaplan-Meier method will be used to estimate the 9 week PFS rate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

at 9 weeks

Results posted on

2017-08-14

Participant Flow

Participant milestones

Participant milestones
Measure	Everolimus + Temozolomide Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	49
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Temozolomide Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Ineligible	1

Baseline Characteristics

Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Temozolomide n=48 Participants Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	60 years n=99 Participants
Sex: Female, Male Female	16 Participants n=99 Participants
Sex: Female, Male Male	32 Participants n=99 Participants
Region of Enrollment United States	48 Participants n=99 Participants

PRIMARY outcome

Timeframe: at 9 weeks

Outcome measures

Outcome measures
Measure	Everolimus + Temozolomide n=48 Participants Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
9-week Progression-free Survival Rate	0.44 proportion of patients Interval 0.29 to 0.59

SECONDARY outcome

Timeframe: Time from registration to death due to any cause; Up to 5 years

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Everolimus + Temozolomide n=48 Participants Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Survival Time	8.6 months Interval 7.1 to 12.2

SECONDARY outcome

Timeframe: Time from registration to the earliest date documentation of disease progression; Up to 5 years

Time to disease progression is defined as the time from registration to the earliest date documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

Outcome measures

Outcome measures
Measure	Everolimus + Temozolomide n=48 Participants Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Time to Disease Progression	2.4 months Interval 2.1 to 4.0

SECONDARY outcome

Timeframe: Up to 5 years

Confirmed response rates will be evaluated by dividing the number of confirmed responders (i.e. patients that achieve a CR or PR on consecutive evaluations) by the total number of evaluable patients. Confidence intervals for the true response rate will be calculated using the properties of the binomial distribution.

Outcome measures

Outcome measures
Measure	Everolimus + Temozolomide n=48 Participants Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Confirmed Response Rate (Complete Response and Partial Response)	8.3 percentage of confirmed responses Interval 2.3 to 20.0

Adverse Events

Everolimus + Temozolomide

Serious events: 6 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus + Temozolomide n=48 participants at risk Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cardiac disorders Palpitations	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Ear, nose and throat examination abnormal	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Death	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fatigue	2.1% 1/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Immune system disorders Hypersensitivity	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Infections and infestations Skin infection	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Leukocyte count decreased	6.2% 3/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Lymphocyte count decreased	4.2% 2/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Neutrophil count decreased	8.3% 4/48 • Number of events 4 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Platelet count decreased	10.4% 5/48 • Number of events 5 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Anorexia	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.1% 1/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Rash desquamating	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.

Other adverse events

Other adverse events
Measure	Everolimus + Temozolomide n=48 participants at risk Patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and 200 mg/m\^2 temozolomide orally once a day on days 8-12 for cycle 1 only (where cycle length is 35 days). For cycle 2 and all subsequent cycles, patients receive 10 mg everolimus orally once a day on days 1-5, 8-12, 15-19, and 22-26 and 200 mg/m\^2 temozolomide orally once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Hemoglobin decreased	16.7% 8/48 • Number of events 14 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Abdominal pain	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Constipation	10.4% 5/48 • Number of events 6 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Diarrhea	14.6% 7/48 • Number of events 8 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Ear, nose and throat examination abnormal	39.6% 19/48 • Number of events 27 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Nausea	56.2% 27/48 • Number of events 40 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Vomiting	27.1% 13/48 • Number of events 16 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Disease progression	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fatigue	81.2% 39/48 • Number of events 116 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Alanine aminotransferase increased	2.1% 1/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Aspartate aminotransferase increased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Bilirubin increased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Creatinine increased	2.1% 1/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Leukocyte count decreased	64.6% 31/48 • Number of events 90 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Lymphocyte count decreased	56.2% 27/48 • Number of events 101 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Neutrophil count decreased	45.8% 22/48 • Number of events 43 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Platelet count decreased	43.8% 21/48 • Number of events 58 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Serum cholesterol increased	8.3% 4/48 • Number of events 8 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Weight loss	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Anorexia	43.8% 21/48 • Number of events 39 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Blood glucose increased	6.2% 3/48 • Number of events 6 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum albumin decreased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum calcium decreased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum calcium increased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum potassium decreased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum potassium increased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum sodium decreased	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Serum triglycerides increased	6.2% 3/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Back pain	6.2% 3/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Joint pain	6.2% 3/48 • Number of events 5 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Muscle weakness	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 3/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 2/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Dizziness	4.2% 2/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Facial nerve disorder	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Headache	29.2% 14/48 • Number of events 22 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Taste alteration	4.2% 2/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Psychiatric disorders Agitation	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Psychiatric disorders Anxiety	6.2% 3/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Psychiatric disorders Depression	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Psychiatric disorders Insomnia	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Renal and urinary disorders Cystitis	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Renal and urinary disorders Urinary frequency	2.1% 1/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Reproductive system and breast disorders Pelvic pain	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Cough	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 2/48 • Number of events 3 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	12.5% 6/48 • Number of events 20 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Body odor	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Erythema multiforme	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Rash acneiform	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Rash desquamating	4.2% 2/48 • Number of events 2 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.
Skin and subcutaneous tissue disorders Urticaria	2.1% 1/48 • Number of events 1 • Adverse events are assessed within 14 days prior to registration and during the Active Monitoring Phase at the start of each treatment cycle; Up to 5 years. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting. All graded adverse events are reported.

Additional Information

Svetomir Markovic, MD, PhD

Mayo Clinic

Phone: 507/284-1370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place