Phase 2
Completed N=153
Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients
Source: ClinicalTrials.gov NCT01234402 ↗Enrolled (actual)
153
Serious AEs
31.1%
Results posted
Aug 2019
Primary outcomePrimary: Progression-Free Survival (PFS) — 22.1; 7.3; 19.0 Weeks — p=0.1315
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) |
22.1; 7.3; 19.0 | 0.1315 |
| SECONDARY Overall Survival (OS) |
67.4; 62.1; 71.6 | 0.0283 sig |
| SECONDARY Percentage of Participants With Objective Response Rate (ORR) |
28.8; 20.4; 34.7 | 0.6691 |
| SECONDARY Duration of Response |
43.1; 20.1; 17.1 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
52; 49; 48 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
20; 25; 6 | — |
| SECONDARY Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab |
308 | — |
| SECONDARY Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab |
23.7; 80.6; 44.7; 65.8; 66.8; 74.3 | — |
| SECONDARY Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab |
54400 | — |
| SECONDARY Terminal Half-life (t½) of Ramucirumab or Icrucumab |
6.80 | — |
| SECONDARY Clearance (Cl) of Ramucirumab or Icrucumab |
0.0141 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab |
3.17 | — |
| SECONDARY Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies |
0; 0 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT01234402). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.