A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00862784
• Collaborator: (none)
• Enrollment: 48
• Locations: 7
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to test how long participants with colorectal cancer live without progressive disease when being treated with IMC-1121B (ramucirumab) and the modified FOLFOX-6 chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Carcinoma	Biological: IMC-1121B (ramucirumab); Drug: Oxaliplatin; Drug: Folinic acid; Drug: 5-FU; Drug: 5-FU	Phase 2

Detailed Description

The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with the monoclonal antibody IMC-1121B (ramucirumab) in combination with the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] chemotherapy regimen as first-line therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter, Phase 2 Study Evaluating the Safety and Efficacy of IMC-1121B in Combination With 5-FU/FA and Oxaliplatin (Modified FOLFOX-6) as First-line Therapy in Patients With Metastatic Colorectal Cancer
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IMC-1121B (ramucirumab) + mFOLFOX-6 This regimen will be repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.

Biological: IMC-1121B (ramucirumab); 8 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) infusions every 2 weeks; Other Names: ramucirumab LY3009806 ; Drug: Oxaliplatin; 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; Drug: Folinic acid; 400 mg/m² intravenous infusion over 2 hours on Day 1; Drug: 5-FU; 400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion; Drug: 5-FU; 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU on Days 1 and 2

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [First dose to measured progressive disease or death due to any cause up to 28.1 months]

   PFS was defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion. For participants who had no PD or death or had started new therapeutic anticancer treatment, PFS was censored at their last radiographic tumor assessment.

Secondary Outcome Measures

1. Percentage of Participants With Complete Response or Partial Response [Objective Response Rate (ORR)] [First dose to date of objective progressive disease up to 23.8 months]

   ORR is the percentage of participants with a confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

2. Overall Survival (OS) [First dose to death due to any cause up to 28.1 months]

   OS was defined as the time from first dose to the date of death due to any cause. For participants who were alive or were lost to follow-up, OS was censored on the last date the participant was known to be alive.

3. Duration of Response [Time of response to time of measured progressive disease up to 22.2 months]

   The duration of response was defined as the time from first objective status assessment of complete response (CR) or partial response (PR) to the first time of progression or death as a result of any cause. CR or PR is classified by the investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion.

4. Number of Participants With IMC-1121B (Ramucirumab)-Related Adverse Events (AEs) [First dose to 25.2 months]

   Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.

5. Number of Participants With IMC-1121B (Ramucirumab)-Related Severe Adverse Events (SAEs) [First dose to 25.2 months]

   Data presented are the number of participants who experienced SAEs, adverse events (AEs) resulting in death and AEs leading to discontinuation of treatment, that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

6. Maximum Concentration (Cmax) at Day 1 of Cycle 1 [Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)]

   Due to sparse pharmacokinetic schedule, Cmax was not calculated.

7. Area Under the Concentration (AUC) at Day 1 of Cycle 1 [Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)]

   Due to sparse pharmacokinetic schedule, AUC was not calculated.

8. Half-Life (t1/2) at Day 1 of Cycle 1 [Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)]

   Due to sparse pharmacokinetic schedule, t1/2 was not calculated.

9. Clearance (CL) at Day 1 of Cycle 1 [Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)]

   Due to sparse pharmacokinetic schedule, CL was not calculated.

10. Steady State Volume of Distribution (Vss) at Day 1 of Cycle 1 [Baseline, 1, 168, and 336 hours post infusion Day 1 (Cycle 1)]

    Due to sparse pharmacokinetic schedule, Vss was not calculated.

11. Maximum Concentration (Cmax) at Day 1 of Cycles 5, 9, 13, 17, and 21 [Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)]

    Due to sparse pharmacokinetic schedule, Cmax was not calculated.

12. Area Under the Concentration (AUC) at Day 1 of Cycles 5, 9, 13, 17, and 21 [Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)]

    Due to sparse pharmacokinetic schedule, AUC was not calculated.

13. Half-Life (t1/2) at Day 1 of Cycles 5, 9, 13, 17, and 21 [Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)]

    Due to sparse pharmacokinetic schedule, t1/2 was not calculated.

14. Clearance (CL) at Day 1 of Cycles 5, 9, 13, 17, and 21 [Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)]

    Due to sparse pharmacokinetic schedule, CL was not calculated.

15. Steady State Volume of Distribution (Vss) at Day 1 of Cycles 5, 9, 13, 17, and 21 [Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)]

    Due to sparse pharmacokinetic schedule, Vss was not calculated.

16. Serum Anti-IMC-1121B (Immunogenicity) at Day 1 [Day 1 (Cycles 1, 5, 9, and 30-day follow-up)]

    Data presented are the number of participants with treatment emergent anti-IMC-112B antibodies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant must have histologically confirmed adenocarcinoma of the colon or rectum that is locally-advanced or metastatic and unresectable

• The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (cm) with conventional techniques or ≥ 1 cm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by Response Evaluation Criteria in Solid Tumors (RECIST)]; target lesion(s) must not lie within an irradiated area. Participants with locally advanced rectal carcinoma who have undergone previous radiation must have documented evidence of disease progression in the pelvis in order to participate

• The participant is age ≥ 18 years

• The participant has a life expectancy of ≥ 6 months

• The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry

• The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1500/microliter (μL), hemoglobin ≥ 10 grams/deciliter (g/dL), and platelets ≥ 100,000/μL

• The participant has adequate hepatic function as defined by: total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (or 5.0 x ULN in the case of liver metastases), and serum albumin ≥ lower limit of normal (LLN) institutional range or (if < LLN) within 10% of the LLN

• The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 60 milliliters/minute (mL/min)

• The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study]

• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin, must have an INR between 2 and 3 and no active bleeding or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)

• The participant has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to Grade 0

• The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment

• The participant has provided signed informed consent

Exclusion Criteria:

• The participant has received prior systemic chemotherapy for locally-advanced unresectable or metastatic colorectal cancer (CRC). Prior adjuvant chemotherapy is allowed if disease progression has been documented > 6 months after the end of the last cycle of adjuvant chemotherapy or > 12 months after the end of the last cycle of adjuvant oxaliplatin-containing regimens

• The participant has documented and/or symptomatic brain or leptomeningeal metastases

• The participant has participated in clinical studies of non-approved experimental agents or procedures within 12 weeks of study entry

• The participant has received previous therapy with monoclonal antibodies

• The participant has received previous therapy with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptor-2 (VEGFR-2) (including multi-targeted tyrosine kinase inhibitors)

• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator

• The participant is on chronic non-topical corticosteroid treatment for > 6 months at doses > 10 mg/day of prednisolone or equivalent before study entry, which in the opinion of the investigator could compromise the participant or the study

• The participant has a known dihydropyrimidine dehydrogenase (DPD) deficiency

• The participant has a known allergy to any of the treatment components

• The participant has an acute or subacute intestinal obstruction

• The participant has uncontrolled or poorly controlled hypertension on a standard regimen of anti-hypertensive therapy

• The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years

• The participant, if female, is pregnant

• Has had prior autologous or allogeneic organ or tissue transplantation

• Has interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the investigator could compromise the participant or the study

• Has pleural effusion or ascites that causes > Grade 1 dyspnea

• Has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent

• Has undergone major surgery within 28 days prior to the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to the first dose of study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
2	ImClone Investigational Site	Toronto	Ontario	Canada	M5G-2M9
3	ImClone Investigational Site	Montreal	Quebec	Canada	H2L 4M1
4	ImClone Investigational Site	Barcelona		Spain
5	ImClone Investigational Site	Santander		Spain
6	ImClone Investigational Site	Seville		Spain
7	ImClone Investigational Site	Valencia		Spain

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00862784
• Other Study ID Numbers: 13897; 2008-004936-19; CP12-0709; I4T-IE-JVBH
• First Posted: Mar 17, 2009
• Last Update Posted: Jun 17, 2014
• Last Verified: May 1, 2014

• Keywords provided by Eli Lilly and Company: Colorectal carcinoma; CRC; Colon Cancer
• Additional relevant MeSH terms: Colorectal Neoplasms; Leucovorin; Folic Acid; Oxaliplatin; Fluorouracil; Ramucirumab; Antibodies, Monoclonal; Levoleucovorin

Study Results

Participant Flow

Pre-assignment Detail	Completer was defined as any participant who died due to any cause or progression of disease, or any participant who was alive and on study but off study treatment at the conclusion of the study.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Period Title: Overall Study
STARTED	48
Received Any Amount of Study Drug	48
COMPLETED	48
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Overall Participants	48
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	31 64.6%
>=65 years	17 35.4%
Sex: Female, Male (Count of Participants)
Female	23 47.9%
Male	25 52.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 10.4%
Not Hispanic or Latino	43 89.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	48 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Canada	5 10.4%
Spain	43 89.6%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion. For participants who had no PD or death or had started new therapeutic anticancer treatment, PFS was censored at their last radiographic tumor assessment.
Time Frame	First dose to measured progressive disease or death due to any cause up to 28.1 months

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug. The number of participants censored was 11.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Median (95% Confidence Interval) [months]	11.5

2. Secondary Outcome

Title	Percentage of Participants With Complete Response or Partial Response [Objective Response Rate (ORR)]
Description	ORR is the percentage of participants with a confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.
Time Frame	First dose to date of objective progressive disease up to 23.8 months

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Number (95% Confidence Interval) [percentage of participants]	58.3 121.5%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from first dose to the date of death due to any cause. For participants who were alive or were lost to follow-up, OS was censored on the last date the participant was known to be alive.
Time Frame	First dose to death due to any cause up to 28.1 months

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug. The number of participants censored was 18.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Median (95% Confidence Interval) [months]	20.4

4. Secondary Outcome

Title	Duration of Response
Description	The duration of response was defined as the time from first objective status assessment of complete response (CR) or partial response (PR) to the first time of progression or death as a result of any cause. CR or PR is classified by the investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion.
Time Frame	Time of response to time of measured progressive disease up to 22.2 months

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug who had CR and PR.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	28
Median (95% Confidence Interval) [months]	11.0

5. Secondary Outcome

Title	Number of Participants With IMC-1121B (Ramucirumab)-Related Adverse Events (AEs)
Description	Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of serious AEs (SAEs) and all other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.
Time Frame	First dose to 25.2 months

Outcome Measure Data

Analysis Population Description

All participants who received at any amount of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Related AEs	45 93.8%
Related AEs of Grade ≥3	19 39.6%
Related AE resulting in death	2 4.2%
Related AE leading to discontinuation	11 22.9%

6. Secondary Outcome

Title	Number of Participants With IMC-1121B (Ramucirumab)-Related Severe Adverse Events (SAEs)
Description	Data presented are the number of participants who experienced SAEs, adverse events (AEs) resulting in death and AEs leading to discontinuation of treatment, that were considered to be related to IMC-1121B (ramucirumab) by the investigators. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	First dose to 25.2 months

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Number [participants]	10 20.8%

7. Secondary Outcome

Title	Maximum Concentration (Cmax) at Day 1 of Cycle 1
Description	Due to sparse pharmacokinetic schedule, Cmax was not calculated.
Time Frame	Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

8. Secondary Outcome

Title	Area Under the Concentration (AUC) at Day 1 of Cycle 1
Description	Due to sparse pharmacokinetic schedule, AUC was not calculated.
Time Frame	Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

9. Secondary Outcome

Title	Half-Life (t1/2) at Day 1 of Cycle 1
Description	Due to sparse pharmacokinetic schedule, t1/2 was not calculated.
Time Frame	Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

10. Secondary Outcome

Title	Clearance (CL) at Day 1 of Cycle 1
Description	Due to sparse pharmacokinetic schedule, CL was not calculated.
Time Frame	Baseline, 1, 168, and 336 hours post infusion on Day 1 (Cycle 1)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

11. Secondary Outcome

Title	Steady State Volume of Distribution (Vss) at Day 1 of Cycle 1
Description	Due to sparse pharmacokinetic schedule, Vss was not calculated.
Time Frame	Baseline, 1, 168, and 336 hours post infusion Day 1 (Cycle 1)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

12. Secondary Outcome

Title	Maximum Concentration (Cmax) at Day 1 of Cycles 5, 9, 13, 17, and 21
Description	Due to sparse pharmacokinetic schedule, Cmax was not calculated.
Time Frame	Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

13. Secondary Outcome

Title	Area Under the Concentration (AUC) at Day 1 of Cycles 5, 9, 13, 17, and 21
Description	Due to sparse pharmacokinetic schedule, AUC was not calculated.
Time Frame	Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

14. Secondary Outcome

Title	Half-Life (t1/2) at Day 1 of Cycles 5, 9, 13, 17, and 21
Description	Due to sparse pharmacokinetic schedule, t1/2 was not calculated.
Time Frame	Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

15. Secondary Outcome

Title	Clearance (CL) at Day 1 of Cycles 5, 9, 13, 17, and 21
Description	Due to sparse pharmacokinetic schedule, CL was not calculated.
Time Frame	Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

16. Secondary Outcome

Title	Steady State Volume of Distribution (Vss) at Day 1 of Cycles 5, 9, 13, 17, and 21
Description	Due to sparse pharmacokinetic schedule, Vss was not calculated.
Time Frame	Baseline and 1 hour post infusion on Day 1 (Cycles 5, 9, 13, 17, and 21)

Outcome Measure Data

Analysis Population Description

No participants were analyzed due to sparse pharmacokinetic schedule.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	0

17. Secondary Outcome

Title	Serum Anti-IMC-1121B (Immunogenicity) at Day 1
Description	Data presented are the number of participants with treatment emergent anti-IMC-112B antibodies.
Time Frame	Day 1 (Cycles 1, 5, 9, and 30-day follow-up)

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study drug and had serum Anti-IMC-1121B (ramucirumab) evaluated.

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
Measure Participants	48
Cycle 1 (n=39)	0 0%
Cycle 5 (n=33)	2 4.2%
Cycle 9 (n=25)	0 0%
30-day Follow-up (n=17)	2 4.2%

Adverse Events

Arm/Group Title	IMC-1121B (Ramucirumab) + mFOLFOX-6
Arm/Group Description	Received IMC-1121B (ramucirumab) 8 milligrams/kilogram (mg/kg) on Day 1 administered intravenously over 60 minutes and followed by administration of the modified FOLFOX-6 [folinic acid (FA) + fluorouracil (5-FU) + oxaliplatin, mFOLFOX-6] regimen as follows: Oxaliplatin 85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1; FA 400 mg/m² intravenous infusion over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus injection over 2 to 4 minutes, immediately following the FA infusion; 5-FU 2400 mg/m² intravenous continuous infusion over 46 hours immediately following bolus 5-FU injection on Days 1 and 2. This regimen was repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
All Cause Mortality
	IMC-1121B (Ramucirumab) + mFOLFOX-6
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IMC-1121B (Ramucirumab) + mFOLFOX-6
	Affected / at Risk (%)	# Events
Total	18/48 (37.5%)
Blood and lymphatic system disorders
COAGULOPATHY	1/48 (2.1%)	1
FEBRILE NEUTROPENIA	1/48 (2.1%)	1
NEUTROPENIA	1/48 (2.1%)	3
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	1/48 (2.1%)	1
CARDIO-RESPIRATORY ARREST	1/48 (2.1%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	1/48 (2.1%)	1
DIARRHOEA	1/48 (2.1%)	1
INTESTINAL OBSTRUCTION	1/48 (2.1%)	1
General disorders
DISEASE PROGRESSION	2/48 (4.2%)	2
PYREXIA	2/48 (4.2%)	2
Infections and infestations
ABDOMINAL ABSCESS	1/48 (2.1%)	1
ANAL ABSCESS	1/48 (2.1%)	1
HAEMOPHILUS INFECTION	1/48 (2.1%)	1
PELVIC ABSCESS	1/48 (2.1%)	1
PNEUMONIA	1/48 (2.1%)	1
UROSEPSIS	1/48 (2.1%)	1
Injury, poisoning and procedural complications
HIP FRACTURE	1/48 (2.1%)	1
Renal and urinary disorders
NEPHROTIC SYNDROME	1/48 (2.1%)	1
Reproductive system and breast disorders
OVARIAN TORSION	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
HYPOXIA	1/48 (2.1%)	1
PULMONARY EMBOLISM	2/48 (4.2%)	2
Vascular disorders
DEEP VEIN THROMBOSIS	1/48 (2.1%)	1
JUGULAR VEIN THROMBOSIS	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	IMC-1121B (Ramucirumab) + mFOLFOX-6
	Affected / at Risk (%)	# Events
Total	47/48 (97.9%)
Blood and lymphatic system disorders
ANAEMIA	8/48 (16.7%)	12
HAEMOGLOBINAEMIA	3/48 (6.3%)	3
LEUKOPENIA	8/48 (16.7%)	22
NEUTROPENIA	27/48 (56.3%)	101
THROMBOCYTOPENIA	17/48 (35.4%)	41
Eye disorders
CONJUNCTIVITIS	4/48 (8.3%)	4
Gastrointestinal disorders
ABDOMINAL PAIN	13/48 (27.1%)	14
CONSTIPATION	10/48 (20.8%)	13
DIARRHOEA	32/48 (66.7%)	150
DYSPEPSIA	5/48 (10.4%)	7
FLATULENCE	3/48 (6.3%)	3
HAEMORRHOIDS	3/48 (6.3%)	3
NAUSEA	21/48 (43.8%)	52
PROCTALGIA	3/48 (6.3%)	6
RECTAL HAEMORRHAGE	4/48 (8.3%)	9
STOMATITIS	8/48 (16.7%)	16
VOMITING	12/48 (25%)	28
General disorders
ASTHENIA	35/48 (72.9%)	154
FATIGUE	4/48 (8.3%)	10
INFUSION RELATED REACTION	9/48 (18.8%)	18
MUCOSAL INFLAMMATION	26/48 (54.2%)	61
OEDEMA PERIPHERAL	11/48 (22.9%)	19
PYREXIA	13/48 (27.1%)	22
Infections and infestations
NASOPHARYNGITIS	5/48 (10.4%)	8
RESPIRATORY TRACT INFECTION	8/48 (16.7%)	11
URINARY TRACT INFECTION	5/48 (10.4%)	10
Investigations
ALANINE AMINOTRANSFERASE INCREASED	3/48 (6.3%)	6
ASPARTATE AMINOTRANSFERASE INCREASED	4/48 (8.3%)	6
GAMMA-GLUTAMYLTRANSFERASE INCREASED	5/48 (10.4%)	9
WEIGHT DECREASED	3/48 (6.3%)	3
Metabolism and nutrition disorders
ANOREXIA	11/48 (22.9%)	15
Musculoskeletal and connective tissue disorders
ARTHRALGIA	5/48 (10.4%)	6
BACK PAIN	7/48 (14.6%)	11
PAIN IN EXTREMITY	4/48 (8.3%)	5
Nervous system disorders
DIZZINESS	3/48 (6.3%)	3
DYSAESTHESIA	23/48 (47.9%)	97
DYSGEUSIA	7/48 (14.6%)	10
HEADACHE	7/48 (14.6%)	11
HYPOAESTHESIA	3/48 (6.3%)	10
NEUROPATHY PERIPHERAL	5/48 (10.4%)	11
NEUROTOXICITY	32/48 (66.7%)	71
PARAESTHESIA	7/48 (14.6%)	12
PERIPHERAL SENSORY NEUROPATHY	5/48 (10.4%)	9
Psychiatric disorders
INSOMNIA	4/48 (8.3%)	4
Renal and urinary disorders
DYSURIA	3/48 (6.3%)	4
HAEMATURIA	3/48 (6.3%)	3
PROTEINURIA	6/48 (12.5%)	10
Respiratory, thoracic and mediastinal disorders
COUGH	5/48 (10.4%)	5
DYSAESTHESIA PHARYNX	6/48 (12.5%)	8
DYSPHONIA	4/48 (8.3%)	5
DYSPNOEA	6/48 (12.5%)	7
EPISTAXIS	15/48 (31.3%)	20
RHINORRHOEA	3/48 (6.3%)	4
Skin and subcutaneous tissue disorders
ALOPECIA	9/48 (18.8%)	10
DERMATITIS ACNEIFORM	4/48 (8.3%)	5
ERYTHEMA	4/48 (8.3%)	7
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	11/48 (22.9%)	22
Vascular disorders
HYPERTENSION	27/48 (56.3%)	42

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.