Trial Outcomes & Findings for Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer (NCT NCT00520481)

NCT ID: NCT00520481

Last Updated: 2018-07-19

Results Overview

cTTP was the time from the first day of treatment to the earliest onset of 1 of the following: tumor progression by Response Evaluation Criteria In Solid Tumors \[RECIST, version 1.0\] criteria: unequivocal evidence of progression by bone scan, new skeletal events, symptomatic progression (for participants without measurable disease), or other clinical events attributable to prostate cancer that in the opinion of the investigator require major interventions. Participants without tumor progression at data cut-off were censored.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

From first dose of study drug until progressive disease (Up to 49.2 months)

Results posted on

2018-07-19

Participant Flow

Participants who had results for the primary outcome measures were considered to have completed the study. The primary outcome measure is: Composite Time to Disease Progression (cTTP) for Participants Treated With Cixutumumab.

Participant milestones

Participant milestones
Measure	IMC-A12 (Cixutumumab) 10 mg/kg Cixutumumab was administered at 10 milligrams/kilogram (mg/kg) as intravenous (i.v.) infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg Cixutumumab was administered at 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Overall Study STARTED	31	10
Overall Study Received at Least 1 Dose of Study Drug	31	10
Overall Study COMPLETED	24	9
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	IMC-A12 (Cixutumumab) 10 mg/kg Cixutumumab was administered at 10 milligrams/kilogram (mg/kg) as intravenous (i.v.) infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg Cixutumumab was administered at 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Overall Study Adverse Event	4	1
Overall Study Withdrawal by Subject	3	0

Baseline Characteristics

Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg /kg n=10 Participants Cixutumumab was administered at 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.	Total n=41 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 9.26 • n=5 Participants	70.2 years STANDARD_DEVIATION 6.78 • n=7 Participants	70.1 years STANDARD_DEVIATION 8.64 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	10 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	10 Participants n=7 Participants	39 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/Ethnicity, Customized White	30 Participants n=5 Participants	10 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants	10 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until progressive disease (Up to 49.2 months)

Population: ITT population: All participants who received at least 1 dose of study drug. Participants censored: Cixutumumab 10 mg/kg =7; or Cixutumumab 20 mg/kg = 2.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Composite Time to Disease Progression (cTTP) for Participants Treated With Cixutumumab	4.9 months Interval 1.9 to 7.0	3.2 months Interval 1.0 to 8.8

PRIMARY outcome

Timeframe: Up to 42 months (predose, 1, 168, 336 and 504 h postdose for Cycles 1 to 4; additionally 24, 72 or 96 h, 120 and 240 or 246 h postdose for Cycle 4; predose and 1 h post dose for Cycles 5 to 9)

Population: Zero participants were analyzed as the data were not estimable accurately due to the study sampling schedule.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 42 months (predose, 1, 168, 336 and 504 h postdose for Cycles 1 to 4; additionally 24, 72 or 96 h, 120 and 240 or 246 h post dose for Cycle 4; predose and 1 h postdose for Cycles 5 to 9)

Population: Participants who received study drug and had evaluable pharmacokinetic (PK) samples for Cmax on Cycle 1 and Cycle 5.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=10 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks After first dose	993 micrograms/milliliter (µg/ml) Geometric Coefficient of Variation 20	—
Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks After fifth dose	1780 micrograms/milliliter (µg/ml) Geometric Coefficient of Variation 53	—

SECONDARY outcome

Timeframe: From randomization up to 49.2 months (and 30 day follow-up)

Population: Safety population: All participants who received any dose of Cixutumumab.

Clinically significant events were defined as SAEs and other non-serious adverse events AEs. Participants who died due to progressive disease (PD), AEs while on treatment or died during the 30 day post-treatment are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) SAEs	6 Participants	0 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Non-serious AEs	28 Participants	10 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Deaths due to PD	1 Participants	0 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Deaths due to AEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until radiographic progression (up to 48.6 months)

Population: ITT population: All participants who received at least 1 dose of study drug. Participants censored: Cixutumumab 10 mg/kg = 9; Cixutumumab 20 mg/kg = 2.

This is the time between first dose and radiographic progression defined as either: progression of measurable or non measurable lesions using the RECIST v 1.0, evidence of progression by bone scan or new skeletal event including new pathologic bone fracture, new bone lesion requiring radiation or surgery, or spinal cord/nerve root compression. Participants without evidence of disease progression at the date of latest tumor or bone radiograph were censored.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Time to Radiographically Evident Disease Progression	4.8 months Interval 1.9 to 7.5	3.3 months Interval 1.9 to 8.8

SECONDARY outcome

Timeframe: From Randomization up to progressive disease (49.2 months)

Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of study drug.

Response was defined using RECIST v1.0 criteria: CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of longest diameter of target lesions

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Number of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Randomization up to 6.21 months

Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of study drug.

Percentage of participants with a PSA decrease of at least 50% from baseline PSA provided the participant had a PSA value of at least 2 nanograms per milliliter (ng/ml) at baseline. Percentage calculated as: (number of participants with PSA response rate / total number of participants) \*100.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate	1.0 Participants	0.0 Participants

SECONDARY outcome

Timeframe: From randomization up to 48.6 months

Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of study drug. Participants censored: Cixutumumab 10 mg/kg - 7; Cixutumumab 20 mg/kg = 2.

PFS rate was the proportion of participants who had stable disease (SD), PR, or CR and were alive at 6 months after receiving their first dose of study medication. Response was defined using RECIST v1.0 criteria: CR was defined as the disappearance of all target lesions, PR was defined as at least a 30% decrease in sum of longest diameter of target lesions, and SD was defined as shrinkage or increase in tumor size that did not meet the above criteria. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. Percentage of participants = (Number of participants with PFS at 6 months / total number of participants analyzed) \*100.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=31 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 Participants Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Progression-Free Survival (PFS) Rate at 6 Months	41.1 percentage of participants Interval 22.3 to 59.0	40.0 percentage of participants Interval 12.3 to 67.0

SECONDARY outcome

Timeframe: Up to 42 months (predose and 1 h postdose for Cycles 1, 5, 9, 13, 17 and 21; additionally immediately following dosing, 168 and 336 h postdose for Cycle 1 only)

Population: Zero participants were analyzed as the data were not estimable accurately due to the study sampling schedule.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 42 months (predose and 1 h postdose for Cycles 1, 5, 9, 13, 17 and 21; additionally immediately following dosing, 168 and 336 h postdose for Cycle 1 only)

Population: Participants who received study drug and had evaluable PK samples for Cmax on Cycle 1 only in 10 mg/kg group.

Outcome measures

Outcome measures
Measure	Cixutumumab 10 mg/kg n=2 Participants Cixutumumab was administered at 10 mg/kg as i.v. infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg Cixutumumab was administered at or 20 mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 10 mg/kg Every 2 Weeks	NA µg/ml Geometric Coefficient of Variation NA Per Clinical Study Report, Cmax was not estimated because of small number of participants with evaluable data (n=2). Individual participant data not provided for data privacy reasons.	—

Adverse Events

Cixutumumab 10 mg/kg

Serious events: 6 serious events

Other events: 28 other events

Deaths: 0 deaths

Cixutumumab 20 mg/kg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cixutumumab 10 mg/kg n=31 participants at risk Cixutumumab was administered at 10 mg/kg as intravenous (i.v.) infusion over 1 hour every 2 weeks until disease progression or intolerable toxicity.	Cixutumumab 20 mg/kg n=10 participants at risk Cixutumumab was administered at 20mg/kg as i.v. infusion over 1 hour every 3 weeks until disease progression or intolerable toxicity.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders DISEASE PROGRESSION	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders FATIGUE	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations PNEUMONIA	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations TROPONIN I INCREASED	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders DEHYDRATION	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders FAILURE TO THRIVE	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders HYPERGLYCAEMIA	6.5% 2/31 • Number of events 2 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders HYPOGLYCAEMIA	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders CEREBROVASCULAR ACCIDENT	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders LEUKOENCEPHALOPATHY	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Renal and urinary disorders RENAL FAILURE	6.5% 2/31 • Number of events 2 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders VERTEBRAL ARTERY OCCLUSION	3.2% 1/31 • Number of events 1 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/10 • From Randomization up to 49.2 months (and 30-day follow-up) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.

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 Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER