Trial Outcomes & Findings for Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma (NCT NCT00199901)

NCT ID: NCT00199901

Last Updated: 2022-10-12

Results Overview

The number of patients who were alive and relapse free 18 months after starting therapy and the number of patients who relapsed or died within 18 months of starting therapy. Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

18 months

Results posted on

2022-10-12

Participant Flow

Patients with resected Stage IIc, lIIb, IIIc and IV melanoma who met eligibility requirements were randomized and stratified by stage of disease to receive 4 intramuscular injections of either NY-ESO-1 ISCOMATRIX® or ISCOMATRIX® adjuvant. The first patient was dosed on 27Sep2005 and the last dose was on 27Jun2007.

111 patients were screened and randomized. One patient did not receive study drug. 56 patients were randomized to the NY-ESO-1 ISCOMATRIX® arm and 54 to the ISCOMATRIX® adjuvant arm.

Participant milestones

Participant milestones
Measure	NY-ESO-1 ISCOMATRIX® Vaccine 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Overall Study STARTED	56	54
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	27	24

Reasons for withdrawal

Reasons for withdrawal
Measure	NY-ESO-1 ISCOMATRIX® Vaccine 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Overall Study Protocol Violation	2	0
Overall Study Withdrawal by Subject	1	0
Overall Study Progressive Disease	24	24

Baseline Characteristics

Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	Total n=110 Participants Total of all reporting groups
Age, Continuous	54.5 years STANDARD_DEVIATION 13.28 • n=5 Participants	53.0 years STANDARD_DEVIATION 13.90 • n=7 Participants	53.7 years STANDARD_DEVIATION 13.54 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	32 Participants n=7 Participants	69 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	54 Participants n=5 Participants	51 Participants n=7 Participants	105 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	56 Participants n=5 Participants	54 Participants n=7 Participants	110 Participants n=5 Participants
Region of Enrollment New Zealand	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United Kingdom	17 participants n=5 Participants	15 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Australia	37 participants n=5 Participants	35 participants n=7 Participants	72 participants n=5 Participants
ECOG ECOG PS 0	51 Participants n=5 Participants	44 Participants n=7 Participants	95 Participants n=5 Participants
ECOG ECOG PS 1	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
ECOG ECOG PS 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG ECOG PS 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG ECOG PS 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Not Recorded	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Rate of Relapse-free Survival at 18 Months Number of patients relapse free at 18 months	29 Participants	28 Participants
Rate of Relapse-free Survival at 18 Months Number of patients relapsed at 18 months	27 Participants	26 Participants

SECONDARY outcome

Timeframe: 18 months

Population: All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Number of Patients With Treatment -Emergent Adverse Events (TEAEs) Number of subjects with at least one TEAE	54 Participants	52 Participants
Number of Patients With Treatment -Emergent Adverse Events (TEAEs) Number of subjects with SAE	10 Participants	12 Participants
Number of Patients With Treatment -Emergent Adverse Events (TEAEs) Number of subjects discontinued due to TEAE	2 Participants	7 Participants

SECONDARY outcome

Timeframe: through study completion; up to 6 years

Population: All patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Relapse-Free Survival During the Entire Period of Observation (up to 6 Years). Number of Patients who did not relapse	23 Participants	25 Participants
Relapse-Free Survival During the Entire Period of Observation (up to 6 Years). Number of patients who relapsed	33 Participants	29 Participants

SECONDARY outcome

Timeframe: through study completion; up to 6 years

Population: All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Overall Survival measured during the entire Period of Observation (up to 6years). Overall survival was measured from start of treatment to the last follow-up or death.

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Overall Survival Number of Patients Alive at last follow-up	32 Participants	31 Participants
Overall Survival Number of Patients Dead at last follow-up	24 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline

Population: All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of \>100,000). The number of patients with each antibody response level are tabulated at each timepoint.

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=46 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=45 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 0	31 Participants	32 Participants
NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 1	2 Participants	0 Participants
NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 2	8 Participants	10 Participants
NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 3	3 Participants	2 Participants
NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 4	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 71

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=43 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=45 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 0	0 Participants	32 Participants
NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 1	0 Participants	2 Participants
NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 2	2 Participants	8 Participants
NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 3	32 Participants	2 Participants
NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 4	9 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 197

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=34 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=32 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 0	0 Participants	20 Participants
NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 1	0 Participants	0 Participants
NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 2	3 Participants	7 Participants
NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 3	21 Participants	5 Participants
NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 4	10 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 365

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=27 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=29 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 0	0 Participants	19 Participants
NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 1	1 Participants	0 Participants
NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 2	3 Participants	6 Participants
NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 3	22 Participants	4 Participants
NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 4	1 Participants	0 Participants

SECONDARY outcome

Timeframe: End of Study (month 18)

Outcome measures

Outcome measures
Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=37 Participants 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=36 Participants 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 0	0 Participants	26 Participants
NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 1	2 Participants	2 Participants
NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 2	6 Participants	4 Participants
NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 3	26 Participants	4 Participants
NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response 4	3 Participants	0 Participants

Adverse Events

NY-ESO-1 ISCOMATRIX® Vaccine

Serious events: 10 serious events

Other events: 54 other events

Deaths: 24 deaths

ISCOMATRIX® Adjuvant

Serious events: 12 serious events

Other events: 52 other events

Deaths: 23 deaths

Serious adverse events

Other adverse events

Additional Information

Jonathan Skipper PhD

Ludwig Institute for Cancer Research

Phone: (212) 450-1539

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	NY-ESO-1 ISCOMATRIX® Vaccine n=56 participants at risk 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	ISCOMATRIX® Adjuvant n=54 participants at risk 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Blood and lymphatic system disorders Anemia	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Gastrointestinal disorders Abdominal neoplasm	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
General disorders Chest pain	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Injury, poisoning and procedural complications Seroma	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Musculoskeletal and connective tissue disorders Radius fracture	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases	3.6% 2/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	5.6% 3/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Skin and subcutaneous tissue disorders Cellulitis	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Skin and subcutaneous tissue disorders Malignant melanoma	3.6% 2/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Skin and subcutaneous tissue disorders Subcutaneous nodule	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Surgical and medical procedures Mass excision	5.4% 3/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	3.7% 2/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Surgical and medical procedures Radioactive iodine therapy	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Surgical and medical procedures Thyroidectomy	1.8% 1/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	0.00% 0/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Vascular disorders Cerebral artery stenosis	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Vascular disorders Transient ischemic attack	0.00% 0/56 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.	1.9% 1/54 • Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug). Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.