Trial Outcomes & Findings for A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) (NCT NCT01286818)
NCT ID: NCT01286818
Last Updated: 2014-10-06
Results Overview
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count \<1.0x10\^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein \>3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
COMPLETED
PHASE1
6 participants
Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
2014-10-06
Participant Flow
Eight (8) participants signed the informed consent.
Participant milestones
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
Completed DLT Assessment Period
|
5
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)
Baseline characteristics by cohort
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
6 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
0 - Fully active
|
3 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
1 - Ambulatory, restricted strenuous activity
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)Population: DLT population: All enrolled participants who either completed the first 3 administrations of study medication or discontinued study medication due to a DLT during the DLT assessment period (Day 1, Cycle 1 through Day 1, Cycle 3).
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count \<1.0x10\^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein \>3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
|
1 participants
|
PRIMARY outcome
Timeframe: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-upPopulation: Safety population: Participants who received any quantity of study medication.
Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. Events related to Irinotecan, Levofolinate, and 5-fluorouracil (5-FU) were reported separately. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Related TEAE
|
6 participants
|
|
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Related SAE
|
0 participants
|
|
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Related Grade ≥3 TEAE
|
3 participants
|
|
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
Related AE leading to discontinuation
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)]Population: Participants who received any quantity of study medication and had evaluable immunogenicity data at the specified time points.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=5 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Day 1, Cycle 5 (n=5)
|
0 participants
|
|
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Day 1, Cycle 6 (n=1)
|
0 participants
|
|
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Day 1, Cycle 7 (n=3)
|
0 participants
|
|
Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)
Day 1, Cycle 9 (n=4)
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)Population: Participants who received any quantity of study medication and had evaluable Cmax data at the specified time points.
The Cmax of ramucirumab in serum on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered Cmax at steady state (Cmax,ss), is reported.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Maximum Concentration (Cmax) of Ramucirumab
Day 1, Cycle 1 (n=6)
|
245 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 6
|
|
Maximum Concentration (Cmax) of Ramucirumab
Day 1, Cycle 5 (n=2)
|
267 micrograms per milliliter (mcg/mL)
Geometric Coefficient of Variation 11
|
SECONDARY outcome
Timeframe: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)Population: Participants who received any quantity of study medication and had evaluable AUC data at the specified time points.
Reported for Day 1, Cycle 1 is AUC from time 0 extrapolated to infinity \[AUC(0-inf)\] and for Day 1, Cycle 5 is AUC over the dosing interval at steady state AUC(tau,ss).
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=4 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Area Under the Curve (AUC) of Ramucirumab
Day 1, Cycle 1 (n=4)
|
1600 micrograms*day/milliliter (mcg*day/mL)
Geometric Coefficient of Variation 15
|
|
Area Under the Curve (AUC) of Ramucirumab
Day 1, Cycle 5 (n=2)
|
1690 micrograms*day/milliliter (mcg*day/mL)
Geometric Coefficient of Variation 38
|
SECONDARY outcome
Timeframe: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)Population: Participants who received any quantity of study medication and had evaluable t1/2 data at the specified time points.
t1/2 is the time required for the plasma/serum concentration to decrease 50%.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Half Life (t1/2) of Ramucirumab
Day 1, Cycle 1 (n=6)
|
7.38 days
Geometric Coefficient of Variation 19
|
|
Half Life (t1/2) of Ramucirumab
Day 1, Cycle 5 (n=2)
|
8.55 days
Geometric Coefficient of Variation 2
|
SECONDARY outcome
Timeframe: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)Population: Participants who received any quantity of study medication and had evaluable CL data at the specified time points.
The total body CL of ramucirumab on Day 1, Cycle 1 and on Day 1, Cycle 5, which was also considered CL at steady state (CLss), is reported.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=4 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Clearance (CL) of Ramucirumab
Day 1, Cycle 1 (n=4)
|
11.4 milliliters per hour (mL/hr)
Geometric Coefficient of Variation 26
|
|
Clearance (CL) of Ramucirumab
Day 1, Cycle 5 (n=2)
|
10.4 milliliters per hour (mL/hr)
Geometric Coefficient of Variation 61
|
SECONDARY outcome
Timeframe: Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days)Population: Participants who received any quantity of study medication and had evaluable Vss data at the specified time points.
Vss is the theoretical volume in which the total amount of study drug would need to be uniformly distributed during steady state to produce the same concentration as it is in plasma/serum.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=4 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Steady State Volume of Distribution (Vss) of Ramucirumab
Day 1, Cycle 1 (n=4)
|
2.51 Liters (L)
Geometric Coefficient of Variation 25
|
|
Steady State Volume of Distribution (Vss) of Ramucirumab
Day 1, Cycle 5 (n=2)
|
3.06 Liters (L)
Geometric Coefficient of Variation 56
|
SECONDARY outcome
Timeframe: Every 8 weeks until PD (up to 49 weeks)Population: Safety population: Participants who received any quantity of study medication.
Best overall response evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression). Stable Disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.
Outcome measures
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 Participants
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Complete Response (CR)
|
0 participants
|
|
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Partial Response (PR)
|
1 participants
|
|
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Stable Disease (SD)
|
4 participants
|
|
Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)]
Progressive Disease (PD)
|
1 participants
|
Adverse Events
FOLFIRI Plus Ramucirumab (IMC-1121B)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
FOLFIRI Plus Ramucirumab (IMC-1121B)
n=6 participants at risk
Ramucirumab (IMC-1121B): Intravenous (IV) infusion, 8 milligrams per kilogram (mg/kg) every 2 weeks. Then 1-hour observation followed by chemotherapy with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) according to manufacturer's standards. Irinotecan: IV infusion, 180 milligrams per square meter (mg/m\^2) every 2 weeks. Levofolinate: IV infusion, 200 mg/m\^2 every 2 weeks. 5-fluorouracil (5-FU): 400 mg/m\^2 bolus followed by a 2400 mg/m\^2 continuous infusion, every 2 weeks.
Antiemetic premedication recommended according to manufacturer's standards but not required prior to ramucirumab drug product infusion. Participants who did not experience unacceptable toxicities during dose limiting toxicity (DLT) assessment period (Day 1, Cycle 1 through Day 1, Cycle 3) who met criteria for treatment continuation received additional cycles of study medication until disease progression, unacceptable toxicity, protocol noncompliance, withdrawal of consent, or Sponsor/investigator decision.
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
16.7%
1/6 • Number of events 3
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
83.3%
5/6 • Number of events 34
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
66.7%
4/6 • Number of events 11
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
16.7%
1/6 • Number of events 2
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
33.3%
2/6 • Number of events 3
|
|
Gastrointestinal disorders
CHEILITIS
|
16.7%
1/6 • Number of events 2
|
|
Gastrointestinal disorders
DIARRHOEA
|
83.3%
5/6 • Number of events 12
|
|
Gastrointestinal disorders
GINGIVITIS
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
LOWER GASTROINTESTINAL HAEMORRHAGE
|
16.7%
1/6 • Number of events 3
|
|
Gastrointestinal disorders
MOUTH HAEMORRHAGE
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
NAUSEA
|
50.0%
3/6 • Number of events 34
|
|
Gastrointestinal disorders
PERIODONTAL DISEASE
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
STOMATITIS
|
83.3%
5/6 • Number of events 12
|
|
Gastrointestinal disorders
VOMITING
|
66.7%
4/6 • Number of events 22
|
|
General disorders
FACE OEDEMA
|
16.7%
1/6 • Number of events 1
|
|
General disorders
FATIGUE
|
50.0%
3/6 • Number of events 5
|
|
General disorders
FEELING ABNORMAL
|
16.7%
1/6 • Number of events 1
|
|
General disorders
INFUSION RELATED REACTION
|
16.7%
1/6 • Number of events 1
|
|
General disorders
MALAISE
|
33.3%
2/6 • Number of events 23
|
|
General disorders
OEDEMA
|
16.7%
1/6 • Number of events 1
|
|
General disorders
OEDEMA PERIPHERAL
|
33.3%
2/6 • Number of events 4
|
|
Infections and infestations
NASOPHARYNGITIS
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
16.7%
1/6 • Number of events 2
|
|
Infections and infestations
URINARY TRACT INFECTION
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
SKIN INJURY
|
16.7%
1/6 • Number of events 1
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
16.7%
1/6 • Number of events 1
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
16.7%
1/6 • Number of events 1
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
16.7%
1/6 • Number of events 1
|
|
Investigations
BLOOD CREATININE INCREASED
|
16.7%
1/6 • Number of events 1
|
|
Investigations
WEIGHT DECREASED
|
16.7%
1/6 • Number of events 2
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
16.7%
1/6 • Number of events 3
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
66.7%
4/6 • Number of events 36
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
16.7%
1/6 • 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 3
|
|
Metabolism and nutrition disorders
HYPOPROTEINAEMIA
|
16.7%
1/6 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
16.7%
1/6 • Number of events 1
|
|
Nervous system disorders
HEADACHE
|
16.7%
1/6 • Number of events 1
|
|
Nervous system disorders
PRESYNCOPE
|
16.7%
1/6 • Number of events 2
|
|
Psychiatric disorders
INSOMNIA
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
PROTEINURIA
|
33.3%
2/6 • Number of events 10
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
50.0%
1/2 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
50.0%
3/6 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
HICCUPS
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
33.3%
2/6 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
16.7%
1/6 • Number of events 2
|
|
Vascular disorders
HYPERTENSION
|
16.7%
1/6 • Number of events 5
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
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