Trial Outcomes & Findings for A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer (NCT NCT00728949)

Last Updated: 2018-06-06

Results Overview

PFS is defined as the time from the date of randomization until date of objectively determined progressive disease (PD) or death due to any cause. 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 unequivocal progression of non-target lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS will be estimated following the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

From randomization up to 35.1 Months

Results posted on

2018-06-06

Participant Flow

Participants who had progressive disease (PD) were considered to complete the study

Participant milestones

Participant milestones
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Overall Study STARTED	62	31
Overall Study COMPLETED	51	27
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Reasons for withdrawal
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Overall Study Adverse Event	8	0
Overall Study Withdrawal by Subject	2	2
Overall Study Abnormal Lab Results	0	2
Overall Study On treatment at cutoff date	1	0

Baseline Characteristics

A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).	Total n=93 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	37 Participants n=5 Participants	24 Participants n=7 Participants	61 Participants n=5 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	7 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	31 Participants n=7 Participants	93 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=5 Participants	30 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	55 Participants n=5 Participants	26 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	62 Participants n=5 Participants	31 Participants n=7 Participants	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization up to 35.1 Months

Population: Intent-to-treat (ITT) population: All randomized participants who were randomized regardless of actual treatment.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Progression-Free Survival (PFS)	2.0 months Interval 1.9 to 3.4	3.1 months Interval 1.9 to 4.2

PRIMARY outcome

Timeframe: From randomization up to 36.5 Months

Population: Intent-to-treat (ITT) population: All randomized participants who were randomized regardless of actual treatment.

OS is defined as the interval between date of randomization and the date of death due to any cause. Participants who are alive at the time of study completion will be censored at the time the participants was last known to be alive.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Overall Survival (OS)	20.3 months Interval 11.5 to Below the level of detection, due to small survival data.	NA months Interval 17.8 to Below the level of detection, due to small survival data.

SECONDARY outcome

Timeframe: Randomization to PD up to 35.1 Months

Population: Intent-to-treat (ITT) population: All randomized participants who were randomized regardless of actual treatment.

Best overall response of CR or PR was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of longest diameter (SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Percentage of Participants With Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])	1.6 percentage of participants Interval 0.0 to 8.7	0 percentage of participants Interval 0.0 to 11.2

SECONDARY outcome

Timeframe: From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 35.1 months

Population: Intent-to-treat (ITT) population: All randomized participants who receive any drug.

The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
12-Month Survival Rate	15 percentage of participants Interval 7.5 to 25.0	7.6 percentage of participants Interval 1.9 to 18.7

SECONDARY outcome

Timeframe: Randomization to PD up to 35.1 Months

Population: Intent-to-treat (ITT) population: All randomized participants who were randomized regardless of actual treatment. Number of participants censored = 15 Cixutumumab + antiestrogen, 5 Cixutumumab only

DCR is defined as percentage of participants with CR, PR, or SD using RECIST v 1.0 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=62 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=31 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Percentage of Participants With Complete Response (CR) and Partial Response (PR) or Stable Disease (SD) Disease Control Rate [DCR])	40.3 percentage of participants Interval 28.1 to 53.6	51.6 percentage of participants Interval 33.1 to 69.8

SECONDARY outcome

Timeframe: Randomization to End of Study up to 36.5 Months

Population: Safety population: All participants who received actual treatment of any drug. There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.

The NCI-CTCAE provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Severity will be graded as mild (grade 1), moderate (grade 2), severe (grade 3), or very severe (life threatening - grade 4). Clinically significant events were defined as serious and other non-serious adverse events related to study drug regardless of causality. A summary of serious and other non-serious adverse events is located in the Reported Adverse Event module.

Outcome measures

Outcome measures
Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=56 Participants Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=37 Participants Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) Participants with SAE's	16 Participants	11 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) AE of greater than Grade 3	22 Participants	19 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) AE with outcome of Death	3 Participants	2 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) Study drug-related AE	48 Participants	31 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) Study drug-related SAE's	5 Participants	2 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) Study drug-related AE of greater than Grade 3	10 Participants	7 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) AE leading to discontinuation of any study drug	6 Participants	1 Participants
Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE) Participants with any AE	55 Participants	36 Participants

SECONDARY outcome

Timeframe: Approximately 24 months

Population: Zero participants analyzed. Circulating tumor cell counts were not collected for analysis.

Outcome measures

Outcome data not reported

Adverse Events

IMC-A12 (Cixutumumab) + Antiestrogen Therapy

Serious events: 16 serious events

Other events: 55 other events

Deaths: 0 deaths

IMC-A12 (Cixutumumab)

Serious events: 11 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	IMC-A12 (Cixutumumab) + Antiestrogen Therapy n=56 participants at risk Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.	IMC-A12 (Cixutumumab) n=37 participants at risk Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Cardiac disorders Pericarditis	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Abdominal pain	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	5.4% 2/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Anal fissure	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Ascites	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Constipation	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Diarrhoea	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Nausea	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	5.4% 2/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Oesophageal pain	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Gastrointestinal disorders Vomiting	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	5.4% 2/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
General disorders Disease progression	3.6% 2/56 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	5.4% 2/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
General disorders Infusion related reaction	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
General disorders Pain	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Hepatobiliary disorders Hepatic cirrhosis	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Infections and infestations Gastroenteritis	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Infections and infestations Gastroenteritis viral	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Infections and infestations Pneumonia	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Injury, poisoning and procedural complications Wrong drug administered	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Metabolism and nutrition disorders Anorexia	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Metabolism and nutrition disorders Dehydration	3.6% 2/56 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Metabolism and nutrition disorders Hyperglycaemia	3.6% 2/56 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 2 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/56 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Musculoskeletal and connective tissue disorders Pathological fracture	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Nervous system disorders Syncope	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	2.7% 1/37 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.8% 1/56 • Number of events 1 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.	0.00% 0/37 There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.