Clinical trial NCT01234402: Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients
Official title: An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or Icrucumab (IMC-18F1) in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-11-04
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with oral capecitabine therapy; capecitabine is administered twice a day on Days 1-14 of each cycle). Approximately 150 participants will be randomized in a 1:1:1 ratio to either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine (Arm A and Arm B, respectively) or capecitabine monotherapy (Arm C). Randomization will be stratified by triple-negative receptor status (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2 \[HER2/neu\]-negative) (yes/no) and receipt of prior antiangiogenic therapy.

Treatment with the study medication(s) will continue until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.


Eligibility criteria: Inclusion Criteria:

* The participant has histologically or cytologically confirmed breast cancer which at the time of study entry is either Stage III disease not amenable to curative therapy or Stage IV disease
* Has measurable or nonmeasurable disease
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Has received prior anthracycline therapy
* Has received prior taxane therapy
* Participants with human epidermal growth factor receptor-2 (HER2) positive disease must have progressed on or following trastuzumab
* Participants with hormone receptor-positive disease must have progressed on or following hormone therapy
* Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as any agent\[s\] that has been administered for more than 1 cycle; sequential neoadjuvant/adjuvant treatment is considered 1 regimen)
* Has completed any prior radiotherapy ≥ 4 weeks prior to randomization
* Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization
* Has adverse events (AEs) that have resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or hormonal therapy
* Has adequate hematologic, coagulation, hepatic and renal function
* Does not have:

  * cirrhosis at a level of Child-Pugh B (or worse) or
  * cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
* Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+, a 24-hour urine collection must demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study
* Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study medication

Exclusion Criteria:

* Has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that there has been a disease-free interval for \> 3 years
* Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
* Has a known sensitivity to 5-fluorouracil (5-FU)
* Has a known dihydropyrimidine dehydrogenase deficiency
* Has received prior capecitabine treatment for advanced breast cancer
* Has received investigational therapy within 2 weeks prior to randomization
* Has received bevacizumab within 4 weeks prior to randomization
* Has received more than 1 prior antiangiogenic agent for breast cancer
* Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or Icrucumab (IMC-18F1), or other agents that specifically target vascular endothelial growth factor (VEGF)
* Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
* Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
* Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization
* Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other oral anticoagulant
* Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorder in the opinion of the investigator
* Has experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomization
* Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
* Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
* Has received a prior allogeneic organ or tissue transplantation
* Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
* Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
* Has known HIV or AIDS infection
* Has an elective or planned major surgery to be performed during the course of the trial
* Participant is pregnant or lactating

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)
measure: Percentage of Participants With Objective Response Rate (ORR)
timeFrame: From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)
measure: Duration of Response
timeFrame: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up To 160 Weeks
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up To 160 Weeks
measure: Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab
timeFrame: Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Terminal Half-life (t½) of Ramucirumab or Icrucumab
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Clearance (Cl) of Ramucirumab or Icrucumab
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
measure: Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies
timeFrame: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: ImClone Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: Jacksonville
country: United States
facility: ImClone Investigational Site
state: Florida
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Augusta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Chicago
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: ImClone Investigational Site
state: Indiana
city: Baton Rouge
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Bronx
country: United States
facility: ImClone Investigational Site
state: New York
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: Stony Brook
country: United States
facility: ImClone Investigational Site
state: New York
city: Washington
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Columbus
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Dallas
country: United States
facility: ImClone Investigational Site
state: Texas
city: San Antonio
country: United States
facility: ImClone Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: ImClone Investigational Site
state: Utah
city: Richmond
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Spokane
country: United States
facility: ImClone Investigational Site
state: Washington
city: Morgantown
country: United States
facility: ImClone Investigational Site
state: West Virginia
city: Calgary
country: Canada
facility: ImClone Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: ImClone Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: ImClone Investigational Site
state: Ontario
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Vahdat LT, Layman R, Yardley DA, Gradishar W, Salkeni MA, Joy AA, Garcia AA, Ward P, Khatcheressian J, Sparano J, Rodriguez G, Tang S, Gao L, Dalal RP, Kauh J, Miller K. Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer. Oncologist. 2017 Mar;22(3):245-254. doi: 10.1634/theoncologist.2016-0265. Epub 2017 Feb 20.