Trial Outcomes & Findings for Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer (NCT NCT00703326)

Last Updated: 2021-12-06

Results Overview

PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available. If death or PD occurred after ≥2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1144 participants

Primary outcome timeframe

Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)

Results posted on

2021-12-06

Participant Flow

Participants who were alive and completed the follow-up period or who died were considered to have completed the study.

Participant milestones

Participant milestones
Measure	Ramucirumab (IMC-1121B) + Docetaxel Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Overall Study STARTED	759	385
Overall Study Received at Least 1 Dose of Study Drug	752	382
Overall Study COMPLETED	657	347
Overall Study NOT COMPLETED	102	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramucirumab (IMC-1121B) + Docetaxel Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Overall Study Lost to Follow-up	47	18
Overall Study Withdrawal by Subject	54	20
Overall Study Adverse Event	1	0

Baseline Characteristics

Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=759 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=385 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Total n=1144 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	629 Participants n=5 Participants	325 Participants n=7 Participants	954 Participants n=5 Participants
Age, Categorical >=65 years	130 Participants n=5 Participants	60 Participants n=7 Participants	190 Participants n=5 Participants
Age, Continuous	53.9 years STANDARD_DEVIATION 10.5 • n=5 Participants	54.2 years STANDARD_DEVIATION 10.0 • n=7 Participants	54.0 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	759 Participants n=5 Participants	385 Participants n=7 Participants	1144 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	69 Participants n=5 Participants	42 Participants n=7 Participants	111 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	690 Participants n=5 Participants	343 Participants n=7 Participants	1033 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	31 Participants n=5 Participants	20 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	27 Participants n=5 Participants	14 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) White	676 Participants n=5 Participants	341 Participants n=7 Participants	1017 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants	9 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment Serbia	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	58 Participants n=5 Participants	21 Participants n=7 Participants	79 Participants n=5 Participants
Region of Enrollment Taiwan	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Slovakia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Spain	118 Participants n=5 Participants	64 Participants n=7 Participants	182 Participants n=5 Participants
Region of Enrollment Lebanon	24 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment Ireland	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Russia	210 Participants n=5 Participants	99 Participants n=7 Participants	309 Participants n=5 Participants
Region of Enrollment Israel	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United Kingdom	21 Participants n=5 Participants	10 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment Egypt	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Czechia	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Canada	83 Participants n=5 Participants	46 Participants n=7 Participants	129 Participants n=5 Participants
Region of Enrollment Poland	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment Belgium	48 Participants n=5 Participants	20 Participants n=7 Participants	68 Participants n=5 Participants
Region of Enrollment Brazil	30 Participants n=5 Participants	20 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment Peru	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Australia	28 Participants n=5 Participants	21 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment South Africa	41 Participants n=5 Participants	22 Participants n=7 Participants	63 Participants n=5 Participants
Region of Enrollment Germany	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment New Zealand	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment South Korea	14 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)

Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=231, placebo + docetaxel=94.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=759 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=385 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Progression-Free Survival (PFS)	9.5 months Interval 8.3 to 9.8	8.2 months Interval 7.1 to 8.5

SECONDARY outcome

Timeframe: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)

Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=267, placebo + docetaxel=121.

OS was defined as the duration from randomization to death from any cause. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=759 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=385 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Overall Survival (OS)	30.3 months Interval 27.5 to 33.5	28.7 months Interval 25.6 to 32.3

SECONDARY outcome

Timeframe: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)

Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=263, placebo + docetaxel=104.

TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who did not progress were censored at the last radiographic tumor assessment. If no post-baseline assessment was available censoring occurred at the date of randomization. If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=759 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=385 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Time to Progression (TTP)	9.7 months Interval 8.5 to 10.3	8.2 months Interval 7.1 to 9.0

SECONDARY outcome

Timeframe: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)

Population: Intent-to-Treat (ITT) Population: All randomized participants.

Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment. CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=759 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=385 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)	44.7 percentage of participants Interval 41.1 to 48.3	37.9 percentage of participants Interval 33.1 to 43.0

SECONDARY outcome

Timeframe: Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)

Population: A subset of the Intent-to-Treat (ITT) Population: all randomized participants with CR or PR. Censored participants: ramucirumab + docetaxel=80, placebo + docetaxel=28.

Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment. CR defined as disappearance of all target and non-target lesions. PR defined as ≥30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions. PD defined as ≥20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of ≥1 new lesion(s). Participants who did not relapse or die censored at day of last radiographic tumor assessment. If death or PD was after ≥2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits. Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=339 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=146 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Duration of Response	8.4 months Interval 8.0 to 9.7	8.1 months Interval 6.8 to 8.9

SECONDARY outcome

Timeframe: Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)

Population: A subset of Intent-to-Treat (ITT) Population: all randomized participants with a valid baseline and end of therapy assessments.

FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL. Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144. Higher scores indicate fewer symptoms and better HR-QoL.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=494 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=251 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy	-6.8 units on a scale Standard Deviation 17.3	-7.0 units on a scale Standard Deviation 16.8

SECONDARY outcome

Timeframe: First dose to study completion (up to 12.3 years)

Population: All randomized participants who received at least 1 dose of study drug.

Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and other NSAEs is located in the Reported Adverse Event module.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=752 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=382 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Number of Participants With Adverse Events Participants with SAEs	285 participants	117 participants
Number of Participants With Adverse Events Participants with NSAEs	737 participants	373 participants

SECONDARY outcome

Timeframe: Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months

Population: All randomized participants who received at least 1 dose of study drug with anti-IMC-1121B antibodies samples collected during the study.

Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=715 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=360 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013	0.8 percentage of participants	0.8 percentage of participants

SECONDARY outcome

Timeframe: Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)

Population: All follow-up participants (additional participants who were available after primary data cut off 31-Mar-13) who received at least 1 dose of study drug with anti-IMC-1121B antibodies samples collected during the study.

Outcome measures

Outcome measures
Measure	Ramucirumab (IMC-1121B) + Docetaxel n=35 Participants Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.	Placebo + Docetaxel n=22 Participants Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016	0 percentage of participants	0 percentage of participants

Adverse Events

Ramucirumab (IMC-1121B) + Docetaxel

Serious events: 285 serious events

Other events: 737 other events

Deaths: 0 deaths

Placebo + Docetaxel

Serious events: 117 serious events

Other events: 373 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

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