Summary

for people ages 18 years and up (full criteria)
at La Jolla, California
study started
estimated completion:
Barbara Parker

Description

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).

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

Details

  • 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.

Keywords

Breast Neoplasms metastatic breast cancer locally advanced, unresectable breast cancer HER2/NEU negative Paclitaxel Albumin-Bound Paclitaxel Cirmtuzumab + Paclitaxel

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 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 ml/min/1.73 m2

  • 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.

You CAN'T join if...

  • 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.

Location

  • University of California, San Diego not yet accepting patients
    La Jolla California 92093 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Barbara Parker, MD
ID
NCT02776917
Phase
Phase 1
Lead Scientist
Barbara Parker
Study Type
Interventional
Last Updated
May 10, 2018