Trial Outcomes & Findings for A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma (NCT NCT00515697)

Last Updated: 2014-06-18

Results Overview

The percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response during therapy is CR or PR/number of participants treated)\*100.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

First dose to date of objective progressive disease or death due to any cause (up to 34 months)

Results posted on

2014-06-18

Participant Flow

This study comprised 3 study periods: pretreatment, treatment, and (posttreatment) follow-up. 40 participants signed the informed consent.

Participant milestones

Participant milestones
Measure	Ramucirumab Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Overall Study STARTED	39
Overall Study Received at Least 1 Dose of Study Drug	39
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Age, Customized Between 18 and 65 years	27 participants n=5 Participants
Age, Customized >=65 years	12 participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Race/Ethnicity, Customized White	35 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants
Ethnicity Hispanic or Latino	1 participants n=5 Participants
Ethnicity Not Hispanic or Latino	38 participants n=5 Participants

PRIMARY outcome

Timeframe: First dose to date of objective progressive disease or death due to any cause (up to 34 months)

Population: Intent-to-treat population: participants who received any quantity of ramucirumab.

Outcome measures

Outcome measures
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Percentage of Participants With Objective Response (Objective Response Rate)	5.1 percentage of participants Interval 0.6 to 17.3

SECONDARY outcome

Timeframe: First dose to measured progressive disease or death due to any cause (up to 34 months)

Population: Intent-to-treat population: participants who received any quantity of ramucirumab. The number of participants censored was 4.

Progression-free survival (PFS) is measured from the date of the first dose to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria or death from any cause. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data for participants whose disease does not progress or for whom no post-baseline assessment is made are censored at the day of their last tumor assessment. Data for participants whose disease does not progress who are subsequently lost to follow-up are also censored at the day of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Progression-Free Survival	7.1 months Interval 4.1 to 9.7

SECONDARY outcome

Timeframe: Week 12 [Cycle 6 (1 cycle=14 days)]

Population: Intent-to-treat population: participants who received any quantity of ramucirumab.

Participants who were alive and did not experience disease progression were considered to have disease control at 12 weeks. Disease control was based on lack of disease progression using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. According to RECIST criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or detection of new lesion. Participants whose disease progression was symptomatic were not considered to have disease control. The percentage of participants showing disease control=(number of participants who did not have disease or symptomatic progression at Week 12/number of participants treated)\*100.

Outcome measures

Outcome measures
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Percentage of Participants Showing Disease Control at Week 12	64.1 percentage of participants Interval 47.2 to 78.8

SECONDARY outcome

Timeframe: Week 12 [Cycle 6 (1 cycle=14 days)]

Population: Intent-to-treat population: participants who received any quantity of ramucirumab.

The percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at Week 12, as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved at 12 weeks was CR or PR/number of participants treated)\*100.

Outcome measures

Outcome measures
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Percentage of Participants With Objective Response (Objective Response Rate) at 12 Weeks	0.0 percentage of participants Interval 0.0 to 9.0

SECONDARY outcome

Timeframe: Time of first response (CR or PR) to disease progression, initiation of other (or additional) antitumor therapy, or death due to any cause (up to 34 months)

Population: Participants who received any quantity of ramucirumab and had confirmed complete response or partial response. The number of participants censored was 1.

Duration of response is the interval from the date of initial documented response \[confirmed complete response (CR) or partial response (PR)\] to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data from participants who did not relapse were censored on the day of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Ramucirumab n=2 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Median Duration of Overall Response	NA months Interval 2.8 to Two participants had confirmed response (1 CR and 1 PR, both occurring more than 12 weeks after starting drug therapy). The participant with CR did not relapse and data were thus censored for the analysis.

SECONDARY outcome

Timeframe: Immediately prior to the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]

Population: Participants who received any quantity of ramucirumab and had evaluable pharmacokinetic data at the specified time point.

Outcome measures

Outcome measures
Measure	Ramucirumab n=11 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Minimum Concentration (Cmin) of Ramucirumab	147 micrograms per milliliter (mcg/mL) Standard Deviation 76.2

SECONDARY outcome

Timeframe: 1 hour after the end of the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]

Population: Participants who received any quantity of ramucirumab and had evaluable pharmacokinetic data at the specified time point.

Outcome measures

Outcome measures
Measure	Ramucirumab n=9 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Maximum Concentration (Cmax) of Ramucirumab	595 micrograms per milliliter (mcg/mL) Standard Deviation 239

SECONDARY outcome

Timeframe: First dose to study completion (up to 34 months) plus 30-day safety follow-up

Population: Intent-to-treat population: participants who received any quantity of ramucirumab.

Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Ramucirumab n=39 Participants Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related TEAE	37 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related SAE	6 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related Grade 3 or 4 TEAE	10 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related AE leading to discontinuation	7 participants

Adverse Events

Ramucirumab

Serious events: 12 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ramucirumab n=39 participants at risk Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Cardiac disorders CARDIO-RESPIRATORY ARREST	2.6% 1/39 • Number of events 1
Cardiac disorders MYOCARDIAL INFARCTION	2.6% 1/39 • Number of events 1
General disorders FATIGUE	2.6% 1/39 • Number of events 1
General disorders MULTI-ORGAN FAILURE	2.6% 1/39 • Number of events 1
Infections and infestations URINARY TRACT INFECTION	2.6% 1/39 • Number of events 1
Metabolism and nutrition disorders ANOREXIA	2.6% 1/39 • Number of events 1
Musculoskeletal and connective tissue disorders BACK PAIN	2.6% 1/39 • Number of events 1
Nervous system disorders ALTERED STATE OF CONSCIOUSNESS	2.6% 1/39 • Number of events 1
Nervous system disorders CEREBRAL ISCHAEMIA	2.6% 1/39 • Number of events 1
Nervous system disorders NEUROPATHY PERIPHERAL	2.6% 1/39 • Number of events 1
Nervous system disorders SPINAL CORD COMPRESSION	2.6% 1/39 • Number of events 1
Renal and urinary disorders HAEMATURIA	2.6% 1/39 • Number of events 1
Renal and urinary disorders PROTEINURIA	2.6% 1/39 • Number of events 1
Renal and urinary disorders RENAL FAILURE ACUTE	2.6% 1/39 • Number of events 1
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	2.6% 1/39 • Number of events 1
Surgical and medical procedures SPINAL LAMINECTOMY	2.6% 1/39 • Number of events 1
Vascular disorders HYPERTENSIVE CRISIS	2.6% 1/39 • Number of events 1

Other adverse events

Other adverse events
Measure	Ramucirumab n=39 participants at risk Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Blood and lymphatic system disorders ANAEMIA	7.7% 3/39 • Number of events 3
Blood and lymphatic system disorders THROMBOCYTOPENIA	12.8% 5/39 • Number of events 8
Eye disorders VISION BLURRED	5.1% 2/39 • Number of events 2
Gastrointestinal disorders ABDOMINAL DISCOMFORT	5.1% 2/39 • Number of events 3
Gastrointestinal disorders ABDOMINAL PAIN	15.4% 6/39 • Number of events 9
Gastrointestinal disorders CONSTIPATION	20.5% 8/39 • Number of events 9
Gastrointestinal disorders DIARRHOEA	17.9% 7/39 • Number of events 16
Gastrointestinal disorders DYSPEPSIA	5.1% 2/39 • Number of events 3
Gastrointestinal disorders ERUCTATION	5.1% 2/39 • Number of events 2
Gastrointestinal disorders FLATULENCE	5.1% 2/39 • Number of events 2
Gastrointestinal disorders NAUSEA	25.6% 10/39 • Number of events 13
Gastrointestinal disorders TOOTHACHE	5.1% 2/39 • Number of events 2
Gastrointestinal disorders VOMITING	23.1% 9/39 • Number of events 10
General disorders CHILLS	15.4% 6/39 • Number of events 7
General disorders FACE OEDEMA	5.1% 2/39 • Number of events 2
General disorders FATIGUE	48.7% 19/39 • Number of events 37
General disorders INFUSION RELATED REACTION	7.7% 3/39 • Number of events 6
General disorders OEDEMA PERIPHERAL	35.9% 14/39 • Number of events 19
General disorders PYREXIA	5.1% 2/39 • Number of events 2
Infections and infestations PHARYNGITIS	7.7% 3/39 • Number of events 7
Infections and infestations RHINITIS	17.9% 7/39 • Number of events 14
Infections and infestations SINUSITIS	5.1% 2/39 • Number of events 3
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	10.3% 4/39 • Number of events 5
Injury, poisoning and procedural complications CONTUSION	7.7% 3/39 • Number of events 3
Investigations BLOOD CREATININE INCREASED	10.3% 4/39 • Number of events 5
Investigations WEIGHT DECREASED	15.4% 6/39 • Number of events 8
Investigations WEIGHT INCREASED	7.7% 3/39 • Number of events 3
Metabolism and nutrition disorders ANOREXIA	25.6% 10/39 • Number of events 13
Metabolism and nutrition disorders DEHYDRATION	5.1% 2/39 • Number of events 2
Metabolism and nutrition disorders HYPERCALCAEMIA	5.1% 2/39 • Number of events 2
Metabolism and nutrition disorders HYPERGLYCAEMIA	7.7% 3/39 • Number of events 4
Metabolism and nutrition disorders HYPERURICAEMIA	5.1% 2/39 • Number of events 5
Metabolism and nutrition disorders HYPOPHOSPHATAEMIA	7.7% 3/39 • Number of events 3
Musculoskeletal and connective tissue disorders ARTHRALGIA	30.8% 12/39 • Number of events 16
Musculoskeletal and connective tissue disorders BACK PAIN	20.5% 8/39 • Number of events 11
Musculoskeletal and connective tissue disorders BONE PAIN	5.1% 2/39 • Number of events 2
Musculoskeletal and connective tissue disorders FLANK PAIN	5.1% 2/39 • Number of events 2
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	7.7% 3/39 • Number of events 4
Musculoskeletal and connective tissue disorders MYALGIA	10.3% 4/39 • Number of events 4
Musculoskeletal and connective tissue disorders NECK PAIN	5.1% 2/39 • Number of events 3
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	10.3% 4/39 • Number of events 5
Nervous system disorders DIZZINESS	10.3% 4/39 • Number of events 6
Nervous system disorders HEADACHE	35.9% 14/39 • Number of events 38
Nervous system disorders NEUROPATHY	5.1% 2/39 • Number of events 2
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	5.1% 2/39 • Number of events 3
Nervous system disorders SOMNOLENCE	5.1% 2/39 • Number of events 2
Psychiatric disorders ANXIETY	10.3% 4/39 • Number of events 4
Psychiatric disorders DEPRESSION	5.1% 2/39 • Number of events 3
Psychiatric disorders INSOMNIA	10.3% 4/39 • Number of events 4
Renal and urinary disorders HAEMATURIA	5.1% 2/39 • Number of events 2
Renal and urinary disorders PROTEINURIA	17.9% 7/39 • Number of events 10
Renal and urinary disorders RENAL FAILURE ACUTE	5.1% 2/39 • Number of events 3
Respiratory, thoracic and mediastinal disorders COUGH	17.9% 7/39 • Number of events 13
Respiratory, thoracic and mediastinal disorders DYSPNOEA	17.9% 7/39 • Number of events 11
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	5.1% 2/39 • Number of events 2
Respiratory, thoracic and mediastinal disorders EPISTAXIS	33.3% 13/39 • Number of events 19
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	5.1% 2/39 • Number of events 3
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	10.3% 4/39 • Number of events 5
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	5.1% 2/39 • Number of events 2
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	5.1% 2/39 • Number of events 2
Skin and subcutaneous tissue disorders DRY SKIN	12.8% 5/39 • Number of events 5
Skin and subcutaneous tissue disorders NIGHT SWEATS	5.1% 2/39 • Number of events 2
Skin and subcutaneous tissue disorders PAIN OF SKIN	5.1% 2/39 • Number of events 2
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	7.7% 3/39 • Number of events 4
Skin and subcutaneous tissue disorders PRURITUS	12.8% 5/39 • Number of events 11
Skin and subcutaneous tissue disorders RASH	10.3% 4/39 • Number of events 5
Vascular disorders HYPERTENSION	17.9% 7/39 • Number of events 8

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