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Study of Cirmtuzumab and Paclitaxel for Metastatic or Locally Advanced, Unresectable Breast Cancer

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ClinicalTrials.gov Identifier: NCT02776917
Recruitment Status : Recruiting
First Posted : May 18, 2016
Last Update Posted : March 29, 2019
Sponsor:
Collaborator:
Oncternal Therapeutics, Inc
Information provided by (Responsible Party):
Barbara Parker, MD, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE May 16, 2016
First Posted Date  ICMJE May 18, 2016
Last Update Posted Date March 29, 2019
Actual Study Start Date  ICMJE August 15, 2018
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
The rate of dose-limiting toxicities during the first 4 weeks of treatment [ Time Frame: Within 4 weeks of starting study treatment ]
The proportion of clinically significant adverse events per CTCAE Version 4.03 at least possibly related to cirmtuzumab or the combination of cirmtuzumab and paclitaxel during the first four weeks of investigational treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: May 17, 2016)
  • Determine the maximum tolerated dose (MTD) [ Time Frame: 2 years ]
  • Determine the rate of dose limiting toxicities (DLTs) [ Time Frame: within 28 days of starting study treatment ]
Change History Complete list of historical versions of study NCT02776917 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • Safety and tolerability of the combination therapy since the start of any study treatment. [ Time Frame: 12 months ]
    Treatment-emergent adverse events beginning from the start of study treatment to six months after study treatment completion.
  • Objective tumor response rate [ Time Frame: 9 months ]
    The proportion of patients with complete and partial tumor responses as assessed by RECIST v1.1
  • Best tumor response rate [ Time Frame: 9 months ]
    The proportion of patients that achieve a response of stable disease or better as assessed by RECIST v1.1
  • Time to progression [ Time Frame: 2 years ]
    The duration of response measured from the time of initial response until documented tumor progression.
  • Measurement of ROR1 expression levels and cancer stem cell populations [ Time Frame: 12 months ]
    Immunohistochemistry measurement of ROR1 expression levels and other cancer stem cell markers (ALDH, CD133) from primary pre-treatment and post-treatment tumor specimens.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2016)
  • Treatment-emergent adverse events [ Time Frame: 5 months ]
  • Objective tumor response [ Time Frame: 4 months ]
  • Time to progression [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Cirmtuzumab and Paclitaxel for Metastatic or Locally Advanced, Unresectable Breast Cancer
Official Title  ICMJE A Phase 1b Pilot Clinical Trial of Cirmtuzumab, an Anti-ROR1 Monoclonal Antibody, in Combination With Paclitaxel for the Treatment of Patients With Metastatic, or Locally Advanced, Unresectable Breast Cancer
Brief Summary 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).
Detailed Description
  • This is a phase 1b, open-label, non-randomized, fixed dose study in patients with HER2 negative metastatic, or locally advanced, unresectable breast cancer.
  • Cirmtuzumab and paclitaxel will be administered until disease progression or unacceptable toxicity. Cirmtuzumab or paclitaxel may be continued alone if the other drug is discontinued due to toxicity, as long as the subject is tolerating the drug and does not exhibit disease progression.
  • Blood and tissue samples will be collected at pre-specified times to enable pharmacokinetic and correlative studies.
  • Adverse events (AE) will be monitored throughout the trial. Reporting of AEs will be in accordance with CTCAE version 4.03.
  • Assessment of tumor response will be performed by physical examination and/or by radiographic imaging and according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
  • Patients will be assessed at 28 days following the last dose of cirmtuzumab to assess tumor response and at 56 days following the last dose of cirmtuzumab to assess any adverse events and to document any concomitant cancer therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE Drug: Cirmtuzumab + Paclitaxel
Cirmtuzumab and paclitaxel may be administered until disease progression or unacceptable toxicity. Cirmtuzumab or paclitaxel may be continued alone if the other drug is discontinued due to toxicity.
Other Name: UC-961, Taxol
Study Arms  ICMJE Experimental: Cirmtuzumab + Paclitaxel

Cirmtuzumab 600 mg is administered intravenously on Days 1 and 15 of the first 28-day cycle, then on Day 1 of each subsequent 28-day cycle.

Paclitaxel 80 mg/m^2 is administered weekly on Days 1, 8, 15, and 22 of each 28-day cycle.

Intervention: Drug: Cirmtuzumab + Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 10, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2016)
12
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  • Biopsy-confirmed, metastatic or locally advanced surgically unresectable, HER2 negative breast cancer. HER2 status should reflect the most recent biopsy results. Note: HER2 negative breast cancer is defined according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2013 for HER2 testing performed in a CLIA-certified laboratory.
  • ER/PR negative (<10% of cells staining for ER or PR) breast cancer or have ER/PR positive (≥10% of cells staining for ER or PR) breast cancer that has exhausted standard endocrine therapy and/or in the opinion of the treating oncologist, warrants cytotoxic chemotherapy.
  • Measurable disease as defined by RECIST v1.1. Measurable lesions will be confirmed by radiographic imaging (CT or MRI). Patients with bone only disease will be eligible if disease is considered measurable and a soft tissue component is present and can be biopsied..
  • There is no limit to prior lines of therapy, but patients must not have received prior taxane chemotherapy in the metastatic setting.
  • ECOG Performance Status ≤ 2.
  • Adequate organ function as defined below:

    • Absolute Neutrophil Count ≥ 1.0 x 10^9/L
    • Platelet count ≥ 100,000 /μL
    • Hemoglobin ≥ 8.0 g/dL
    • Total bilirubin ≤ 1.5 x upper limit of normal
    • AST and ALT ≤ 3 x upper limit of normal
    • Serum creatinine ≤ 2 x upper limit of normal OR Creatinine clearance > 40 ml/min/1.73 m^2
  • Women of child-bearing potential and male subjects who are sexually active with a woman of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months following last infusion of cirmtuzumab. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Existing neuropathy must be no greater than Grade 1.
  • No concurrent antibody therapy can be planned with the exception of denosumab for use in bone metastasis.
  • CNS metastases are allowed as long as the metastases are asymptomatic, have been treated with radiation, and have been stable for > 6 weeks off steroids.

EXCLUSION CRITERIA:

  • Patient is currently receiving chemotherapy or has received another chemotherapy within 5 half-lives, radiotherapy or immunotherapy within 2 weeks prior to study treatment initiation.
  • Patient has known, untreated and/or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Patient had disease that was refractory to paclitaxel in the neoadjuvant setting and/or developed metastatic breast cancer within 6 months of neoadjuvant or adjuvant taxane chemotherapy.
  • Patient has had major surgery within 3 weeks prior to enrollment.
  • Patient 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 active infection).
  • The patient has known acute or chronic hepatitis B or C.
  • The patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel.
  • The patient 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.
  • Patient has a history of non-compliance or other medical illness that would preclude compliance with study procedures.
  • Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  • Patient has severe cardiac insufficiency (NYHA III or IV) with uncontrolled and/or unstable cardiac or coronary artery disease
  • Patient is pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barbara Parker, MD 858-822-6135 baparker@ucsd.edu
Contact: Rebecca Shatsky, MD 858-657-7000 rshatsky@ucsd.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02776917
Other Study ID Numbers  ICMJE 160178
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Barbara Parker, MD, University of California, San Diego
Study Sponsor  ICMJE Barbara Parker, MD
Collaborators  ICMJE Oncternal Therapeutics, Inc
Investigators  ICMJE
Principal Investigator: Barbara Parker, MD University of California, San Diego
PRS Account University of California, San Diego
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP