Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01234402
• Other study ID #: 13944
• Secondary ID: CP20-0903I4Y-IE-
• Status: Completed
• Phase: Phase 2
• Start date: March 2011
• Est. completion date: July 2017

Study information

• Verified date: July 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: July 2017
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• Ramucirumab DP
10 mg/kg I.V. Day 1 of every-21-day cycle
• IMC-18F1
12 mg/kg I.V. Days 1 and 8 of every-21-day cycle

Drug:
• Capecitabine
1000 mg/m^2 orally Twice a day for 14 days

Locations

Country	Name	City	State
Canada	ImClone Investigational Site	Calgary	Alberta
Canada	ImClone Investigational Site	Edmonton	Alberta
Canada	ImClone Investigational Site	Toronto	Ontario
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Augusta	Georgia
United States	ImClone Investigational Site	Baton Rouge	Louisiana
United States	ImClone Investigational Site	Bronx	New York
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Cincinnati	Ohio
United States	ImClone Investigational Site	Columbus	Ohio
United States	ImClone Investigational Site	Dallas	Texas
United States	ImClone Investigational Site	Indianapolis	Indiana
United States	ImClone Investigational Site	Jacksonville	Florida
United States	ImClone Investigational Site	Los Angeles	California
United States	ImClone Investigational Site	Morgantown	West Virginia
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Richmond	Virginia
United States	ImClone Investigational Site	Salt Lake City	Utah
United States	ImClone Investigational Site	San Antonio	Texas
United States	ImClone Investigational Site	Scottsdale	Arizona
United States	ImClone Investigational Site	Spokane	Washington
United States	ImClone Investigational Site	Stony Brook	New York
United States	ImClone Investigational Site	Washington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as =20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of =5 millimeter (mm) and the appearance of =1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.	From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Secondary	Overall Survival (OS)	Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive.	From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)
Secondary	Percentage of Participants With Objective Response Rate (ORR)	The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as =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. Disease progression is defined as =20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of =5 mm and the appearance of =1 new lesions was progression.	From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)
Secondary	Duration of Response	Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for progressive disease (PD) is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as =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.PD defined as =20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of =5 mm, or the appearance of 1 or more new lesions was considered progression.	From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Secondary	Number of Participants With Adverse Events (AEs)	Adverse event (AE) will be regarded as treatment-emergent if onset date occurs any time on or after the administration of the first dose of study treatment up to 30 days after the last dose of study treatment (or up to any time if related to study treatment); or it occurs prior to first dose date and worsens while on therapy or up to 30 days after the last dose of study treatment (or up to any time if related to study treatment).; A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Up To 160 Weeks
Secondary	Number of Participants With Serious Adverse Events (SAEs)	SAE was defined as any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening; Required inpatient hospitalization or caused prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Required intervention to prevent permanent impairment/damage; Was an important medical event (defined as a medical event that may not have been immediately life-threatening or resulted in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes listed in the definition above).; A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Up To 160 Weeks
Secondary	Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab		Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab	Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab.	Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab	Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity of Ramucirumab and Icrucumab.	Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Terminal Half-life (t½) of Ramucirumab or Icrucumab	Terminal half-life (t½) of Ramucirumab and Icrucumab.	Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Clearance (Cl) of Ramucirumab or Icrucumab	Clearance (Cl) of Ramucirumab and Icrucumab.	Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab	Volume of Distribution at Steady State (Vss) of Ramucirumab and Icrucumab.	Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Secondary	Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies		Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion