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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02776917
Recruitment Status : Recruiting
First Posted : May 18, 2016
Last Update Posted : August 17, 2018
Oncternal Therapeutics, Inc
Information provided by (Responsible Party):
Barbara Parker, MD, University of California, San Diego

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).

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Cirmtuzumab + Paclitaxel Phase 1

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 via intravenous (IV) infusion weekly during treatment up to six 28-day cycles. Paclitaxel alone may be continued after cirmtuzumab has been discontinued if the patient is receiving benefit.
  • 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 15, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Cirmtuzumab + Paclitaxel

Cirmtuzumab 600 mg is administered intravenously on Days 1 and 15 of each 28-day cycle.

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

Drug: Cirmtuzumab + Paclitaxel
Cirmtuzumab may be administered up to six cycles. Paclitaxel may be continued after cirmtuzumab is stopped.
Other Name: UC-961, Taxol

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. Objective tumor response rate [ Time Frame: 9 months ]
    The proportion of patients with complete and partial tumor responses as assessed by RECIST v1.1

  3. 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

  4. Time to progression [ Time Frame: 2 years ]
    The duration of response measured from the time of initial response until documented tumor progression.

  5. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Metastatic or locally advanced, unresectable, Her2 negative breast cancer. Her2 status should reflect the most recent biopsy results.
  • Triple negative breast cancer, or ER/PR positive breast cancer that has exhausted standard endocrine therapy and/or in the opinion of the treating oncologist, warrants cytotoxic chemotherapy.
  • Measurable or evaluable disease as defined by RECIST v1.1. Subjects with bone only disease will be eligible if disease is considered measurable.
  • Subject has not 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 ≤ 1.25 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 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.
  • Existing neuropathy must be no greater than Grade 1.
  • Concurrent antibody therapy, 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:

  • Subject must not have received taxane based chemotherapy in the metastatic setting (paclitaxel, docetaxel or nab-paclitaxel). Prior neoadjuvant/and or adjuvant taxane chemotherapy is allowed, as long as disease did not relapse/or recur within 6 months of taxane based therapy.
  • Breast cancer that was refractory to paclitaxel in the neoadjuvant setting and/or relapse/disease recurrence within 6 months of neoadjuvant or adjuvant taxane chemotherapy.
  • Current chemotherapy or chemotherapy within 5 half-lives, or radiotherapy or another investigational agent within 4 weeks prior to study treatment initiation.
  • Untreated and/or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Major surgery within 3 weeks prior to enrollment.
  • 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).
  • Known acute or chronic hepatitis B or C.
  • History of allergic reactions to paclitaxel.
  • Known second primary malignancy within 2 years prior to study entry, except curatively treated non-melanotic skin cancer, cervical carcinoma in situ or stage I colon cancer.
  • History of non-compliance or other medical illness that would preclude compliance with study procedures.
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Known severe cardiac insufficiency (NYHA III or IV) with uncontrolled and/or unstable cardiac or coronary artery disease.
  • Subject is pregnant or nursing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02776917

Contact: Barbara Parker, MD 858-822-6135
Contact: Rebecca Shatsky, MD 858-657-7000

United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Jillian McCarthy, MPH    858-822-4516   
Sponsors and Collaborators
Barbara Parker, MD
Oncternal Therapeutics, Inc
Principal Investigator: Barbara Parker, MD University of California, San Diego

Responsible Party: Barbara Parker, MD, Clinical Professor of Medicine, University of California, San Diego Identifier: NCT02776917     History of Changes
Other Study ID Numbers: 160178
First Posted: May 18, 2016    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Barbara Parker, MD, University of California, San Diego:
metastatic breast cancer
locally advanced, unresectable breast cancer
HER2/NEU negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action