This is a pilot phase 1b study to investigate the safety and side effects of combining the
ROR1-targeting monoclonal antibody, cirmtuzumab, with paclitaxel for patients with HER2
negative, metastatic breast cancer. Cirmtuzumab is a type of drug called a monoclonal
antibody. This drug is designed to attach to a protein called receptor-tyrosine-kinase like
orphan receptor 1 (ROR1) on the surface of breast cancer cells. Cirmtuzumab blocks the growth
and survival of the breast cancer cells in laboratory tests. ROR1 is rarely expressed on
healthy cells. Cirmtuzumab is considered experimental and is not approved by United States
(U.S.) Food and Drug Administration (FDA).
- Brief Title: Study of Cirmtuzumab and Paclitaxel for Metastatic or Locally Advanced, Unresectable Breast Cancer
- Official Title: A Phase 1 Clinical Trial to Determine the Safety and Tolerability of Cirmtuzumab, an Anti-ROR1 Monoclonal Antibody, in Combination With Paclitaxel for the Treatment of Patients With Metastatic or Locally Advanced Unresectable Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
- NCT ID:
|Cirmtuzumab + Paclitaxel||UC-961, Taxol||Cirmtuzumab + Paclitaxel|
The purpose of the study is to investigate the safety of the investigational drug called
cirmtuzumab in combination with the breast cancer drug paclitaxel. Cirmtuzumab is a type of
drug called a monoclonal antibody. This drug is designed to attach to a protein called ROR1
that is on the surface of breast cancer cells. This blocks growth and survival of the breast
cancer cells. ROR1 is rarely expressed on healthy cells so this drug should target the cancer
cells. Cirmtuzumab is considered experimental because its use is not approved by United
States (U.S.) Food and Drug Administration (FDA).
Although there is evidence from tests on laboratory animals that cirmtuzumab can decrease the
number of breast cancer cells, we do not know if this will work in humans. This drug has been
tested in humans before, but has never been tested in patients with breast cancer, or in
combination with paclitaxel in humans. Therefore, the goal of this study is to see if
cirmtuzumab is safe and tolerable, when in given in combination with paclitaxel in study
participants. You will be evaluated to find out what effects (good and bad) cirmtuzumab has
on you and we would like to learn more about how cirmtuzumab might affect the growth of your
cancer cells. We would also like to see how long the drug stays in your body and what affects
the drug may have on your body.
This is a Phase 1, open-label, non-randomized, dose escalation study in patients with Her2
negative metastatic or locally advanced, unresectable breast cancer who have not previously
received paclitaxel in the metastatic setting.
All patients providing informed consent will be screened for eligibility. Baseline
assessments will include vital signs, physical exam, blood hematology and chemistries, ECOG
Performance Status evaluation, a bone scan and tumor assessment by physical exam and/or CT
scan of the chest/abdomen/pelvis. Patients who are eligible and proceed with study
participation will be asked to provide an optional tumor sample for correlative studies
within 30 days prior to study treatment initiation.
Cirmtuzumab will be administered via intravenous infusion every two weeks (i.e., Day 1 and
Day 15 of a 28-day cycle). Two dosing cohorts are planned and the starting dose will 8 mg/kg
and 16 mg/kg. The 8 mg/kg dose has been tested and found to be safe in patients with CLL.
Patients will receive four doses of cirmtuzumab unless the patient exhibits disease
progression or unacceptable toxicity. Paclitaxel 80 mg/m2 is administered weekly by
intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle. Patients may discontinue
study treatment if they have progressive disease, are experiencing unacceptable toxicity,
withdraw consent, or if the treating physician determines it's in their best interest.
Patients may also continue to receive paclitaxel after cirmtuzumab has been discontinued.
Clinical evaluation of history and symptoms, physical exams, and vitals will be performed on
Days 1 and 15 of each cycle, and blood draws for laboratory work will be performed weekly
during treatment. Blood draws for pharmacokinetics will occur on Days 1 and 2 of Cycle 1.
Patients will be asked to provide a second optional tumor sample for correlative studies
15-30 days after Cycle 2 Day 15.
An end of treatment visit for clinical evaluations and safety assessments will be performed
approximately 28 days after the last dose of cirmtuzumab. Tumor response will be assessed
approximately 56 days after the last dose of cirmtuzumab by physical exam and/or CT scan of
the chest/abdomen/pelvis, and a bone scan if applicable. A follow-up assessment for adverse
events will occur approximately 84 days after the last dose of cirmtuzumab.
|Cirmtuzumab + Paclitaxel||Experimental||Cirmtuzumab is administered by intravenous infusion on Days 1 and 15 of each 28-day cycle at the dose level for the corresponding subject cohort:
Dose Level 1: 8 mg/kg. Dose Level 2: 16 mg/kg.
Paclitaxel 80 mg/m^2 is administered weekly by intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle.|
- Subject has biopsy-confirmed metastatic or locally advanced surgically unresectable
Her2 negative breast cancer. Her2 status should reflect the most recent biopsy
- Subject has measurable or evaluable disease as defined by RECIST v1.1. Measurable
lesions will be confirmed by radiographic imaging (CT or MRI).
- Subject has not received prior paclitaxel in the metastatic setting.
- Subject is ≥ 18 years of age.
- Subject has ECOG Performance Status ≤ 2.
- Subject has adequate organ function as defined below:
- Absolute Neutrophil Count ≥ 1.0 x 109/L
- Platelet count ≥ 100,000 /μL
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.25 x upper limit of normal
- AST and ALT ≤ 2 x upper limit of normal
- Serum creatinine ≤ 2 x upper limit of normal OR Creatinine clearance> 40
- Women of childbearing potential must agree not to become pregnant for the duration of
- If applicable to the subject, existing neuropathy must be no greater than Grade 1.
- Subject is not planning concurrent antibody therapy, with the exception of denosumab
for use in bone metastasis.
- If applicable to the subject, CNS metastases are allowed as long as the metastases are
asymptomatic, have been treated with radiation, and have been stable for > 6 weeks off
- Subject is currently receiving chemotherapy or has received another chemotherapy
within 5 half-lives, or radiotherapy or another investigational agent within 4 weeks
prior to study treatment initiation.
- Subject has known, untreated and/or symptomatic central nervous system (CNS)
metastases and/or carcinomatous meningitis.
- Subject has had major surgery within 3 weeks prior to enrollment.
- Subject has severe and/or uncontrolled medical disease(s) (i.e., myocardial infarction
within 6 months of study, CKD stage IV or above, severe chronic pulmonary disease or
- Subject has known acute or chronic hepatitis B or C.
- Subject has a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to paclitaxel.
- Subject has a history of another malignancy within 2 years prior to study entry,
except curatively treated non-melanotic skin cancer, cervical carcinoma in situ or
stage I colon cancer.
- Subject has a history of non-compliance or other medical illness that would preclude
compliance with study procedures.
- Subject has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Subject has severe cardiac insufficiency (NYHA III or IV) with uncontrolled and/or
unstable cardiac or coronary artery disease
- Subject is pregnant or nursing.
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||Determine the maximum tolerated dose (MTD)|
|Time Frame:||2 years|
Secondary Outcome Measures
|Measure:||Treatment-emergent adverse events|
|Time Frame:||5 months|
|Measure:||Objective tumor response|
|Time Frame:||4 months|
|Measure:||Time to progression|
|Time Frame:||2 years|
|Overall Status:||Not yet recruiting|
|Lead Sponsor:||Barbara Parker, MD|
- metastatic breast cancer
- locally advanced, unresectable breast cancer
- HER2/NEU negative
May 10, 2017