Trial Outcomes & Findings for A Study of Ramucirumab and Docetaxel in Participants With Solid Tumors (NCT NCT01567163)

NCT ID: NCT01567163

Last Updated: 2014-10-16

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
• Results posted on: 2014-10-16

Participant Flow

Participant milestones

Measure	All Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle Cycle 2: ramucirumab 10-milligrams/kilogram (mg/kg) intravenous infusion, followed by docetaxel 75-mg/m\^2 intravenous infusion administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle
Overall Study STARTED	22
Overall Study Received at Least 1 Dose of Study Drug	22
Overall Study Drug-Drug Interaction Population	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	All Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle Cycle 2: ramucirumab 10-milligrams/kilogram (mg/kg) intravenous infusion, followed by docetaxel 75-mg/m\^2 intravenous infusion administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle
Overall Study Progressive Disease	2
Overall Study Lost to Follow-up	2

Baseline Characteristics

A Study of Ramucirumab and Docetaxel in Participants With Solid Tumors

Baseline characteristics by cohort

Measure	All Participants n=22 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle Cycle 2: ramucirumab 10-milligrams/kilogram (mg/kg) intravenous infusion, followed by docetaxel 75-mg/m\^2 intravenous infusion administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

Population: All participants who completed Cycle 1, Day 1 and Cycle 2, Day 1 treatment and had sufficient concentration data to calculate docetaxel AUC(0-∞) in Cycle 1.

Outcome measures

Measure	Docetaxel (Cycle 1) n=17 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1	13.7 nanograms*hour/milliliter/milligram Geometric Coefficient of Variation 40

PRIMARY outcome

Timeframe: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

Population: All participants who completed Cycle 1, Day 1 and Cycle 2, Day 1 treatment and had sufficient concentration data to calculate docetaxel AUC(0-∞) in Cycle 2.

Outcome measures

Measure	Docetaxel (Cycle 1) n=16 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2	12.8 nanograms*hour/milliliter/milligram Geometric Coefficient of Variation 30

PRIMARY outcome

Timeframe: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48, and 72 hours post docetaxel infusion

Population: All participants who completed Cycle 1, Day 1 and Cycle 2, Day 1 treatment and had sufficient concentration data to calculate docetaxel Cmax in Cycle 1.

Outcome measures

Measure	Docetaxel (Cycle 1) n=17 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1	7.66 nanograms/milliliter/milligram Geometric Coefficient of Variation 76

PRIMARY outcome

Timeframe: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

Population: All participants who completed Cycle 1, Day 1 and Cycle 2, Day 1 treatment and had sufficient concentration data to calculate docetaxel Cmax in Cycle 2.

Outcome measures

Measure	Docetaxel (Cycle 1) n=17 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2	8.78 nanograms/milliliter/milligram Geometric Coefficient of Variation 37

SECONDARY outcome

Timeframe: Cycle 1, Day 1 through Cycle 2, Day 1 and 30 days after last dose of study drug

Population: All participants who completed Cycle 1, Day 1 and Cycle 2, Day 1 treatment who had immunogenicity samples collected at the specified time points.

Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Outcome measures

Measure	Docetaxel (Cycle 1) n=17 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies Immunogenicity During Study (n=17)	0 participants
Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies Immunogenicity Post-Treatment (n=5)	0 participants

SECONDARY outcome

Timeframe: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion

Population: All enrolled participants who received ramucirumab and had sufficient concentration data to calculate ramucirumab AUC(0-∞) in Cycle 2.

Outcome measures

Measure	Docetaxel (Cycle 1) n=11 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel	42400 micrograms*hour/milliliter (mcg*h/mL) Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion

Population: All enrolled participants who received ramucirumab and had sufficient concentration data to calculate ramucirumab Cmax in Cycle 2.

Outcome measures

Measure	Docetaxel (Cycle 1) n=18 Participants Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel	303.6 micrograms/milliliter (mcg/mL) Geometric Coefficient of Variation 28

Adverse Events

All Participants

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Participants n=22 participants at risk Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle Cycle 2: ramucirumab 10-milligrams/kilogram (mg/kg) intravenous infusion, followed by docetaxel 75-mg/m\^2 intravenous infusion administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle
Blood and lymphatic system disorders Febrile neutropenia	18.2% 4/22 • Number of events 4
Blood and lymphatic system disorders Neutropenia	4.5% 1/22 • Number of events 1
Eye disorders Vision blurred	4.5% 1/22 • Number of events 1
Gastrointestinal disorders Abdominal pain	4.5% 1/22 • Number of events 1
Gastrointestinal disorders Constipation	4.5% 1/22 • Number of events 1
Gastrointestinal disorders Diarrhoea	4.5% 1/22 • Number of events 1
General disorders Fatigue	4.5% 1/22 • Number of events 1
General disorders Pyrexia	9.1% 2/22 • Number of events 2
Hepatobiliary disorders Cholecystitis	4.5% 1/22 • Number of events 1
Infections and infestations Bacteraemia	4.5% 1/22 • Number of events 1
Infections and infestations Cellulitis	4.5% 1/22 • Number of events 2
Infections and infestations Clostridium difficile infection	4.5% 1/22 • Number of events 1
Infections and infestations Gastroenteritis	4.5% 1/22 • Number of events 1
Infections and infestations Pneumonia	9.1% 2/22 • Number of events 2
Infections and infestations Wound infection	4.5% 1/22 • Number of events 1
Metabolism and nutrition disorders Dehydration	4.5% 1/22 • Number of events 1
Musculoskeletal and connective tissue disorders Muscular weakness	9.1% 2/22 • Number of events 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	4.5% 1/22 • Number of events 1
Nervous system disorders Nervous system disorder	4.5% 1/22 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.1% 2/22 • Number of events 3
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.5% 1/22 • Number of events 4
Vascular disorders Embolism	4.5% 1/22 • Number of events 1

Other adverse events

Measure	All Participants n=22 participants at risk Cycle 1: docetaxel 75-milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of 3-week cycle Cycle 2: ramucirumab 10-milligrams/kilogram (mg/kg) intravenous infusion, followed by docetaxel 75-mg/m\^2 intravenous infusion administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle
Blood and lymphatic system disorders Anaemia	27.3% 6/22 • Number of events 11
Blood and lymphatic system disorders Neutropenia	18.2% 4/22 • Number of events 4
Gastrointestinal disorders Abdominal pain upper	9.1% 2/22 • Number of events 2
Gastrointestinal disorders Constipation	18.2% 4/22 • Number of events 4
Gastrointestinal disorders Diarrhoea	18.2% 4/22 • Number of events 8
Gastrointestinal disorders Dyspepsia	9.1% 2/22 • Number of events 2
Gastrointestinal disorders Dysphagia	9.1% 2/22 • Number of events 2
Gastrointestinal disorders Nausea	54.5% 12/22 • Number of events 13
Gastrointestinal disorders Oral pain	13.6% 3/22 • Number of events 3
Gastrointestinal disorders Stomatitis	13.6% 3/22 • Number of events 5
Gastrointestinal disorders Vomiting	9.1% 2/22 • Number of events 2
General disorders Asthenia	9.1% 2/22 • Number of events 3
General disorders Chest discomfort	18.2% 4/22 • Number of events 4
General disorders Chills	9.1% 2/22 • Number of events 2
General disorders Fatigue	40.9% 9/22 • Number of events 15
General disorders Oedema peripheral	9.1% 2/22 • Number of events 4
General disorders Pain	9.1% 2/22 • Number of events 2
Infections and infestations Vulvovaginal mycotic infection	11.1% 1/9 • Number of events 1
Investigations Aspartate aminotransferase increased	9.1% 2/22 • Number of events 2
Investigations Blood alkaline phosphatase increased	9.1% 2/22 • Number of events 2
Investigations Neutrophil count decreased	18.2% 4/22 • Number of events 7
Investigations White blood cell count decreased	40.9% 9/22 • Number of events 15
Metabolism and nutrition disorders Decreased appetite	22.7% 5/22 • Number of events 7
Metabolism and nutrition disorders Dehydration	9.1% 2/22 • Number of events 3
Metabolism and nutrition disorders Hyperglycaemia	27.3% 6/22 • Number of events 6
Metabolism and nutrition disorders Hypoalbuminaemia	13.6% 3/22 • Number of events 3
Metabolism and nutrition disorders Hyponatraemia	27.3% 6/22 • Number of events 6
Musculoskeletal and connective tissue disorders Arthralgia	9.1% 2/22 • Number of events 7
Musculoskeletal and connective tissue disorders Muscle spasms	13.6% 3/22 • Number of events 6
Musculoskeletal and connective tissue disorders Myalgia	13.6% 3/22 • Number of events 3
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 2/22 • Number of events 2
Nervous system disorders Dysgeusia	22.7% 5/22 • Number of events 7
Nervous system disorders Headache	18.2% 4/22 • Number of events 4
Nervous system disorders Neuropathy peripheral	13.6% 3/22 • Number of events 4
Psychiatric disorders Insomnia	9.1% 2/22 • Number of events 2
Reproductive system and breast disorders Vaginal haemorrhage	22.2% 2/9 • Number of events 2
Respiratory, thoracic and mediastinal disorders Cough	27.3% 6/22 • Number of events 6
Respiratory, thoracic and mediastinal disorders Dysphonia	9.1% 2/22 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnoea	27.3% 6/22 • Number of events 9
Respiratory, thoracic and mediastinal disorders Epistaxis	13.6% 3/22 • Number of events 4
Respiratory, thoracic and mediastinal disorders Hiccups	9.1% 2/22 • Number of events 2
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.1% 2/22 • Number of events 2
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 2/22 • Number of events 2
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	13.6% 3/22 • Number of events 3
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	9.1% 2/22 • Number of events 2
Skin and subcutaneous tissue disorders Alopecia	22.7% 5/22 • Number of events 5
Skin and subcutaneous tissue disorders Nail discolouration	9.1% 2/22 • Number of events 2
Skin and subcutaneous tissue disorders Nail disorder	9.1% 2/22 • Number of events 3
Skin and subcutaneous tissue disorders Night sweats	9.1% 2/22 • Number of events 2
Skin and subcutaneous tissue disorders Rash	13.6% 3/22 • Number of events 4
Vascular disorders Hypertension	31.8% 7/22 • Number of events 8
Vascular disorders Hypotension	9.1% 2/22 • Number of events 2

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