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.
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.
Brief Title
Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Breast Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01234402
Org Class
Industry
Org Full Name
Eli Lilly and Company
Org Study Id
13944
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Progression-Free Survival (PFS)
Outcome Time Frame
From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Secondary Ids
Secondary Id
CP20-0903
Secondary Id
I4Y-IE-JCDD
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)
Outcome Measure
Overall Survival (OS)
Outcome Description
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.
Outcome Time Frame
From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)
Outcome Measure
Percentage of Participants With Objective Response Rate (ORR)
Outcome Description
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.
Outcome Time Frame
From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Outcome Measure
Duration of Response
Outcome Description
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.
A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Outcome Time Frame
Up To 160 Weeks
Outcome Measure
Number of Participants With Adverse Events (AEs)
Outcome Description
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.
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.
Outcome Time Frame
Up To 160 Weeks
Outcome Measure
Number of Participants With Serious Adverse Events (SAEs)
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab
Outcome Description
Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab.
Outcome Time Frame
Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab
Outcome Description
Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity of Ramucirumab and Icrucumab.
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab
Outcome Description
Terminal half-life (t½) of Ramucirumab and Icrucumab.
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Terminal Half-life (t½) of Ramucirumab or Icrucumab
Outcome Description
Clearance (Cl) of Ramucirumab and Icrucumab.
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Clearance (Cl) of Ramucirumab or Icrucumab
Outcome Description
Volume of Distribution at Steady State (Vss) of Ramucirumab and Icrucumab.
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab
Outcome Time Frame
Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion
Outcome Measure
Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404