Trial Outcomes & Findings for A Study of Ramucirumab (IMC-1121B) in Participants With Breast Cancer (NCT NCT01256567)
NCT ID: NCT01256567
Last Updated: 2014-06-18
Results Overview
Number participants with drug related dose-limiting toxicities (DLT) during Cycle 1; ramucirumab related: treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or higher TEAE, or TEAE leading to discontinuation or ramucirumab dose modification. DLT=G4 neutropenia \>7days; G ≥3 neutropenia with fever ≥38.5°C requiring IV antibiotics or bacteriemia or sepsis; G4 thrombocytopenia; G ≥3 thrombocytopenia with bleeding requiring platelets; G≥3 prothrombin time and/or partial thromboplastin time in absence of anticoagulants; G≥2 hyperbilirubinemia ≥5 days; QTc \>500 milliseconds (ms) or increase ≥100 ms or arrhythmia; G≥4 or uncontrollable hypertension; G≥3 nonhematologic toxicity (excluding G3: hypersensitivity, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea without loperamide therapy, nausea/vomiting without antiemetics, transient G3/4 elevation of aminotransferases); treatment delay \>2 weeks due to toxicity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
7 participants
Primary outcome timeframe
Baseline up to data cut off (approximately 48.3 weeks)
Results posted on
2014-06-18
Participant Flow
Participant milestones
| Measure |
Ramucirumab and Docetaxel Combination
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab (IMC-1121B) administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
7
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Ramucirumab and Docetaxel Combination
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab (IMC-1121B) administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study of Ramucirumab (IMC-1121B) in Participants With Breast Cancer
Baseline characteristics by cohort
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Age, Customized
Between 20 and 65 years
|
6 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
1 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to data cut off (approximately 48.3 weeks)Population: All participants who received at least 1 dose of study drug.
Number participants with drug related dose-limiting toxicities (DLT) during Cycle 1; ramucirumab related: treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or higher TEAE, or TEAE leading to discontinuation or ramucirumab dose modification. DLT=G4 neutropenia \>7days; G ≥3 neutropenia with fever ≥38.5°C requiring IV antibiotics or bacteriemia or sepsis; G4 thrombocytopenia; G ≥3 thrombocytopenia with bleeding requiring platelets; G≥3 prothrombin time and/or partial thromboplastin time in absence of anticoagulants; G≥2 hyperbilirubinemia ≥5 days; QTc \>500 milliseconds (ms) or increase ≥100 ms or arrhythmia; G≥4 or uncontrollable hypertension; G≥3 nonhematologic toxicity (excluding G3: hypersensitivity, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea without loperamide therapy, nausea/vomiting without antiemetics, transient G3/4 elevation of aminotransferases); treatment delay \>2 weeks due to toxicity.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Number of Participants With Adverse Events
Dose Limiting Toxicity (DLT) during Cycle 1
|
2 participants
|
|
Number of Participants With Adverse Events
TEAE related to ramucirumab
|
7 participants
|
|
Number of Participants With Adverse Events
SAE related to ramucirumab
|
4 participants
|
|
Number of Participants With Adverse Events
TEAE of Grade ≥3 related to ramucirumab
|
6 participants
|
|
Number of Participants With Adverse Events
TEAE resulting in ramucirumab discontinuation
|
3 participants
|
|
Number of Participants With Adverse Events
TEAE with ramucirumab dose modification/delay
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline up to data cut off (approximately 48.3 weeks)Population: All participants with evaluable antibody assessment data.
The number of participants with a positive anti-IMC-1121B titer at any point during the study.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Serum Anti-IMC-1121B Antibody Assessment (Immunogenicity)
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)Population: All participants with evaluable Cmax data at the specified time points.
Cmax (Cycle 1) and Cmax at steady state (Cmax,ss, Cycle 4) of ramucirumab are provided.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Maximum Concentration (Cmax) of Ramucirumab
Cmax at Cycle 1
|
261 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 22
|
|
Maximum Concentration (Cmax) of Ramucirumab
Cmax,ss at Cycle 4 (n=6)
|
335 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 22
|
SECONDARY outcome
Timeframe: Day 1 of Cycles 1 and 4 (cycle=21 days)Population: All participants with evaluable AUC data at the specified time points.
AUC from time zero to infinity (AUC\[0-inf\], Cycle 1) and at steady state (AUC tau, Cycle 4) of ramucirumab are provided.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Area Under the Curve (AUC) of Ramucirumab
AUC(0-inf) at Cycle 1
|
1700 micrograms*day/milliliter (mcg*day/mL)
Geometric Coefficient of Variation 25
|
|
Area Under the Curve (AUC) of Ramucirumab
AUC tau at Cycle 4 (n=6)
|
2320 micrograms*day/milliliter (mcg*day/mL)
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: Day 1 of Cycles 1 and 4 (cycle=21 days)Population: All participants with evaluable t1/2 data at the specified time points.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Half Life (t 1/2) of Ramucirumab
t1/2 at Cycle 1
|
6.57 days
Geometric Coefficient of Variation 49
|
|
Half Life (t 1/2) of Ramucirumab
t1/2 at Cycle 4 (n=6)
|
11.9 days
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)Population: All participants with evaluable clearance data at the specified time points.
Clearance (Cycle 1) and at steady state (Clss, Cycle 4) of ramucirumab are provided.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Clearance (Cl) of Ramucirumab
Clearance at Cycle 1
|
13.6 milliliters per hour (mL/hr)
Geometric Coefficient of Variation 24
|
|
Clearance (Cl) of Ramucirumab
Clearance at steady state (Clss) at Cycle 4 (n=6)
|
10.2 milliliters per hour (mL/hr)
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 1 and 4 (cycle=21 days)Population: All participants with evaluable Vss data at the specified time points.
Outcome measures
| Measure |
Ramucirumab and Docetaxel Combination
n=7 Participants
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Steady State Volume of Distribution (Vss) of Ramucirumab
Vss at Cycle 1
|
2.96 liters (L)
Geometric Coefficient of Variation 32
|
|
Steady State Volume of Distribution (Vss) of Ramucirumab
Vss at Cycle 4 (n=6)
|
3.92 liters (L)
Geometric Coefficient of Variation 18
|
Adverse Events
Ramucirumab and Docetaxel Combination
Serious events: 7 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ramucirumab and Docetaxel Combination
n=7 participants at risk
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
42.9%
3/7 • Number of events 3
|
|
Cardiac disorders
Cardiac failure
|
14.3%
1/7 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
14.3%
1/7 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
14.3%
1/7 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
28.6%
2/7 • Number of events 2
|
Other adverse events
| Measure |
Ramucirumab and Docetaxel Combination
n=7 participants at risk
Docetaxel: Docetaxel administered by intravenous infusion at a dose of 75 milligrams per square meter (mg/m\^2) every 3 weeks.
Ramucirumab: Ramucirumab administered as an intravenous infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
14.3%
1/7 • Number of events 3
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
42.9%
3/7 • Number of events 9
|
|
Cardiac disorders
Palpitations
|
14.3%
1/7 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
14.3%
1/7 • Number of events 1
|
|
Ear and labyrinth disorders
Ear pain
|
14.3%
1/7 • Number of events 1
|
|
Eye disorders
Asthenopia
|
14.3%
1/7 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
14.3%
1/7 • Number of events 2
|
|
Eye disorders
Lacrimation increased
|
42.9%
3/7 • Number of events 3
|
|
Eye disorders
Myodesopsia
|
14.3%
1/7 • Number of events 1
|
|
Eye disorders
Visual impairment
|
14.3%
1/7 • Number of events 2
|
|
Gastrointestinal disorders
Ascites
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Cheilitis
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
28.6%
2/7 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
28.6%
2/7 • Number of events 4
|
|
Gastrointestinal disorders
Gingival bleeding
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Gingivitis
|
28.6%
2/7 • Number of events 8
|
|
Gastrointestinal disorders
Haemorrhoids
|
28.6%
2/7 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
28.6%
2/7 • Number of events 3
|
|
Gastrointestinal disorders
Periodontitis
|
14.3%
1/7 • Number of events 2
|
|
Gastrointestinal disorders
Stomatitis
|
42.9%
3/7 • Number of events 9
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7 • Number of events 2
|
|
General disorders
Chest discomfort
|
14.3%
1/7 • Number of events 2
|
|
General disorders
Face oedema
|
57.1%
4/7 • Number of events 6
|
|
General disorders
Fatigue
|
28.6%
2/7 • Number of events 4
|
|
General disorders
Infusion related reaction
|
14.3%
1/7 • Number of events 1
|
|
General disorders
Infusion site extravasation
|
14.3%
1/7 • Number of events 1
|
|
General disorders
Injection site pain
|
14.3%
1/7 • Number of events 1
|
|
General disorders
Malaise
|
57.1%
4/7 • Number of events 19
|
|
General disorders
Mucosal inflammation
|
57.1%
4/7 • Number of events 9
|
|
General disorders
Oedema peripheral
|
100.0%
7/7 • Number of events 16
|
|
General disorders
Pyrexia
|
28.6%
2/7 • Number of events 3
|
|
Infections and infestations
Cystitis
|
14.3%
1/7 • Number of events 4
|
|
Infections and infestations
Nasopharyngitis
|
71.4%
5/7 • Number of events 8
|
|
Injury, poisoning and procedural complications
Fall
|
14.3%
1/7 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
28.6%
2/7 • Number of events 4
|
|
Investigations
Aspartate aminotransferase increased
|
28.6%
2/7 • Number of events 3
|
|
Investigations
Blood urine
|
14.3%
1/7 • Number of events 1
|
|
Investigations
Haematocrit decreased
|
14.3%
1/7 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
28.6%
2/7 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
71.4%
5/7 • Number of events 17
|
|
Investigations
Platelet count decreased
|
14.3%
1/7 • Number of events 4
|
|
Investigations
Platelet count increased
|
14.3%
1/7 • Number of events 2
|
|
Investigations
Weight increased
|
14.3%
1/7 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
14.3%
1/7 • Number of events 2
|
|
Investigations
White blood cell count increased
|
14.3%
1/7 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
42.9%
3/7 • Number of events 10
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
14.3%
1/7 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
14.3%
1/7 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Coccydynia
|
14.3%
1/7 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.3%
1/7 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
28.6%
2/7 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
14.3%
1/7 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma
|
14.3%
1/7 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
57.1%
4/7 • Number of events 10
|
|
Nervous system disorders
Headache
|
28.6%
2/7 • Number of events 3
|
|
Nervous system disorders
Lacunar infarction
|
14.3%
1/7 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
28.6%
2/7 • Number of events 3
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
42.9%
3/7 • Number of events 5
|
|
Nervous system disorders
Presyncope
|
14.3%
1/7 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
42.9%
3/7 • Number of events 5
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
85.7%
6/7 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
85.7%
6/7 • Number of events 12
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
28.6%
2/7 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Eczema
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis palmaris and plantaris
|
14.3%
1/7 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
71.4%
5/7 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
28.6%
2/7 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Rash
|
28.6%
2/7 • Number of events 5
|
|
Vascular disorders
Hypertension
|
14.3%
1/7 • Number of events 1
|
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