Trial Outcomes & Findings for Study of Weekly Paclitaxel With Ramucirumab in Participants With Advanced Gastric Adenocarcinomas (NCT NCT01253525)

Last Updated: 2014-06-18

Results Overview

DLT based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v4.02) in Cycle (Cy) 1 due to study drug (SD) with (w/): Grade (Gr) ≥3 neutropenia w/fever ≥38.5°C or w/bacteremia or sepsis, thrombocytopenia w/bleeding and platelet substitution, prothrombin and/or partial thromboplastin time w/no anticoagulation, hyperbilirubinemia; Gr 4: neutropenia \>5 days, thrombocytopenia, Gr 4 or uncontrollable hypertension QTc\>500 milliseconds (ms) or increase ≥100 ms increase in 24 hours after SD or significant arrhythmia in this period; Gr ≥3 nonhematologic toxicity (tox), excluding Gr 3 hypersensitivity, hypertension, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea w/out loperamide/nausea/vomiting w/out antiemetic and transient aminotransferase elevation. SD tox=delay \>1 week in ramucirumab (RAM) dose or omission of 1 dose of RAM or 2 paclitaxel doses due to tox in Cy 1 or delay \>2 weeks between Cy 1 and Cy 2 due to persistent tox.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

Cycle 1 of 28-day cycle

Results posted on

2014-06-18

Participant Flow

Participants were considered completed if they either completed Cycle 1 of study drug or discontinued study drug due to a dose limiting toxicity (DLT) during Cycle 1.

Participant milestones

Participant milestones
Measure	Ramucirumab + Paclitaxel Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Overall Study STARTED	6
Overall Study Received Any Quantity of Study Drug	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Weekly Paclitaxel With Ramucirumab in Participants With Advanced Gastric Adenocarcinomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Age, Continuous	57.6 years STANDARD_DEVIATION 15.50 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 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	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 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 Japan	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 of 28-day cycle

Population: All enrolled participants who complete the first cycle of study drug or discontinued study drug due to a DLT during Cycle 1.

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1	0 participants

PRIMARY outcome

Timeframe: Up to 47 weeks post baseline

Population: All enrolled participants who received any quantity of study drug.

The number of participants who experienced AEs of any grade, AEs of Grade ≥3 or AEs resulting in death that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of serious adverse events (SAEs) and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Number of Participants With Adverse Events (AEs) RAM-Related AEs Any Grade	6 participants
Number of Participants With Adverse Events (AEs) PAC-Related AEs Any Grade	6 participants
Number of Participants With Adverse Events (AEs) RAM-Related AEs Any Grade ≥3	2 participants
Number of Participants With Adverse Events (AEs) PAC-Related AEs Any Grade ≥3	4 participants
Number of Participants With Adverse Events (AEs) RAM-Related AEs Resulting in Death	0 participants
Number of Participants With Adverse Events (AEs) PAC-Related AEs Resulting in Death	0 participants

PRIMARY outcome

Timeframe: Up to 47 weeks post baseline

Population: All enrolled participants who received any quantity of study drug.

The number of participants who experienced SAEs that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of SAEs and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Number of Participants With Serious Adverse Events (SAEs) RAM-Related SAEs	2 participants
Number of Participants With Serious Adverse Events (SAEs) PAC-Related SAEs	2 participants

SECONDARY outcome

Timeframe: Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable Cmax values.

Cmax after a single dose of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 1	176 micrograms/milliliter (µg/mL) Standard Deviation 46.6

SECONDARY outcome

Timeframe: Cycle 1 through Cycle 5 (28-day cycles)

Population: All enrolled participants who received at least 1 dose of study drug and were analyzed for anti-ramucirumab (IMC-1121B) antibodies.

The percentage of participants who were treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies.

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=6 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)	0 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable AUC0-∞ values.

AUC from time 0 to infinity (0-∞) after a single dose of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=1 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 1	34100 microgramshour/milliliter (µgh/mL) Standard Deviation NA Standard deviation cannot be calculated with results from 1 participant.

SECONDARY outcome

Timeframe: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable t1/2 values.

Terminal t1/2 (the time it takes for the concentration of ramucirumab (IMC-1121B) in plasma or serum to decline by 50%) after a single dose of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=4 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Half-Life (t1/2) for Cycle 1	190 hours (h) Interval 138.0 to 225.0

SECONDARY outcome

Timeframe: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable CL values.

CL \[the volume of plasma or serum cleared of ramucirumab (IMC-1121B) per unit time\] after a single dose of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=1 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Clearance (CL) or Cycle 1	0.0166 liters/hour (L/h) Standard Deviation NA Standard deviation cannot be calculated with results from 1 participant analyzed.

SECONDARY outcome

Timeframe: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable Vss values.

Vss \[distribution of ramucirumab (IMC-1121B) in the body at steady state\] after a single dose of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=1 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 1	3.27 liters (L) Standard Error NA Standard deviation cannot be calculated with results from 1 participant analyzed.

SECONDARY outcome

Timeframe: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable Cmax values.

Cmax after multiple doses of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=4 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 2	284 micrograms/milliliter (µg/mL) Standard Deviation 39.7

SECONDARY outcome

Timeframe: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable AUC 0-τ values.

AUC within the dosing interval (0-τ) after multiple doses of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=2 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 2	41900 microgramshour/milliliter (µgh/mL) Standard Deviation 951

SECONDARY outcome

Timeframe: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable t1/2 values.

Terminal t1/2 \[the time it takes for the concentration of ramucirumab (IMC-1121B) in plasma or serum to decline by 50%\] after multiple doses of ramucirumab(IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=1 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Half-Life (t1/2) for Cycle 2	218 hours (h) Interval 218.0 to 218.0

SECONDARY outcome

Timeframe: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Population: All enrolled participants who received any quantity of study drug and had evaluable CL values.

CL \[the volume of plasma or serum cleared of ramucirumab (IMC-1121B) per unit time\] at steady state after multiple doses of ramucirumab (IMC-1121B).

Outcome measures

Outcome measures
Measure	Ramucirumab + Paclitaxel n=2 Participants Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Ramucirumab Clearance (CL) for Cycle 2	0.0136 liters/hour (L/h) Standard Deviation 0.000342

Adverse Events

Ramucirumab + Paclitaxel

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ramucirumab + Paclitaxel n=6 participants at risk Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Gastrointestinal disorders Gastrointestinal haemorrhage	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Intestinal obstruction	16.7% 1/6 • Number of events 1
Infections and infestations Pneumonia	33.3% 2/6 • Number of events 2
Metabolism and nutrition disorders Decreased appetite	16.7% 1/6 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	16.7% 1/6 • Number of events 1
Nervous system disorders Meningism	16.7% 1/6 • Number of events 7

Other adverse events

Other adverse events
Measure	Ramucirumab + Paclitaxel n=6 participants at risk Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) administered intravenously on Days 1 and 15 of each 28-day cycle. Paclitaxel: 80 milligrams/square meter (mg/m2) administered intravenously on Days 1, 8, and 15 of each 28-day cycle.
Blood and lymphatic system disorders Anaemia	33.3% 2/6 • Number of events 5
Blood and lymphatic system disorders Leukopenia	16.7% 1/6 • Number of events 3
Blood and lymphatic system disorders Lymphopenia	16.7% 1/6 • Number of events 1
Blood and lymphatic system disorders Neutropenia	66.7% 4/6 • Number of events 7
Ear and labyrinth disorders Hearing impaired	16.7% 1/6 • Number of events 1
Eye disorders Retinal haemorrhage	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Number of events 4
Gastrointestinal disorders Haemorrhoidal haemorrhage	33.3% 2/6 • Number of events 2
Gastrointestinal disorders Nausea	50.0% 3/6 • Number of events 5
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 5
General disorders Face oedema	16.7% 1/6 • Number of events 1
General disorders Fatigue	33.3% 2/6 • Number of events 4
General disorders Oedema peripheral	16.7% 1/6 • Number of events 2
General disorders Pyrexia	50.0% 3/6 • Number of events 6
Immune system disorders Hypersensitivity	16.7% 1/6 • Number of events 1
Infections and infestations Lung infection	16.7% 1/6 • Number of events 1
Infections and infestations Onychomycosis	16.7% 1/6 • Number of events 1
Injury, poisoning and procedural complications Skin laceration	16.7% 1/6 • Number of events 1
Investigations Alanine aminotransferase increased	33.3% 2/6 • Number of events 2
Investigations Aspartate aminotransferase increased	33.3% 2/6 • Number of events 2
Investigations Blood alkaline phosphatase increased	16.7% 1/6 • Number of events 1
Investigations Blood lactate dehydrogenase increased	16.7% 1/6 • Number of events 1
Investigations Blood urine present	16.7% 1/6 • Number of events 1
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 2
Investigations Platelet count decreased	33.3% 2/6 • Number of events 3
Investigations Weight decreased	16.7% 1/6 • Number of events 1
Investigations White blood cell count decreased	33.3% 2/6 • Number of events 6
Metabolism and nutrition disorders Decreased appetite	50.0% 3/6 • Number of events 4
Metabolism and nutrition disorders Hyperglycaemia	33.3% 2/6 • Number of events 2
Metabolism and nutrition disorders Hyperuricaemia	16.7% 1/6 • Number of events 1
Metabolism and nutrition disorders Hypoalbuminaemia	16.7% 1/6 • Number of events 1
Metabolism and nutrition disorders Hyponatraemia	33.3% 2/6 • Number of events 2
Metabolism and nutrition disorders Hypophosphataemia	16.7% 1/6 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • Number of events 2
Musculoskeletal and connective tissue disorders Muscular weakness	16.7% 1/6 • Number of events 1
Nervous system disorders Headache	33.3% 2/6 • Number of events 2
Nervous system disorders Neuropathy peripheral	16.7% 1/6 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	33.3% 2/6 • Number of events 2
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1
Renal and urinary disorders Haematuria	16.7% 1/6 • Number of events 1
Renal and urinary disorders Proteinuria	50.0% 3/6 • Number of events 4
Respiratory, thoracic and mediastinal disorders Dysphonia	16.7% 1/6 • Number of events 1
Respiratory, thoracic and mediastinal disorders Epistaxis	83.3% 5/6 • Number of events 8
Respiratory, thoracic and mediastinal disorders Hiccups	16.7% 1/6 • Number of events 1
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 1/6 • Number of events 1
Skin and subcutaneous tissue disorders Alopecia	50.0% 3/6 • Number of events 3
Skin and subcutaneous tissue disorders Onychoclasis	16.7% 1/6 • Number of events 1
Skin and subcutaneous tissue disorders Rash	66.7% 4/6 • Number of events 6
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 1/6 • Number of events 1
Vascular disorders Hot flush	16.7% 1/6 • Number of events 3
Vascular disorders Hypertension	33.3% 2/6 • Number of events 3

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