Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Ramucirumab DP; IMC-18F1; Capecitabine
Intervention description: 10 mg/kg I.V.
Day 1 of every-21-day cycle; 12 mg/kg I.V.
Days 1 and 8 of every-21-day cycle; 1000 mg/m^2 orally
Twice a day for 14 days
Intervention MeSH terms: Capecitabine; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

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