Fresolimumab and Radiotherapy in Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by New York University School of Medicine
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01401062
First received: July 20, 2011
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to test safety of combining fresolimumab and local radiotherapy and to see if the combination can achieve tumor regression.


Condition Intervention
Metastatic Breast Cancer
Drug: fresolimumab (GC1008)
Radiation: Radiation Therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Fresolimumab and Radiotherapy in Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Percentage of Participants with Adverse Events [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Physical exam every 2 weeks while on trial and at 3 monthly follow up visits will monitor patients for Adverse events using the NCI CTCAE vers. 4.0.


Secondary Outcome Measures:
  • Local response rate [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Responses will be assessed at week 5 and week 15 of the trial by PET/CT. Tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). Criteria as described by the European Organisation for Research and Treatment of Cancer (EORTC) PET study group will be used to assess response based on standard uptake value (SUV).


Estimated Enrollment: 28
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
1 mg/kg
Drug: fresolimumab (GC1008)
Fresolimumab is administered intravenously (i.v.) at a dose of 1mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 to lesion 2).
Radiation: Radiation Therapy
7.5 Gy/Fraction for 3 days week 1 and 7.5 Gy/Fraction for 3 days week 7
Experimental: Arm 2
10 mg/kg
Drug: fresolimumab (GC1008)
Fresolimumab is administered i.v. at a dose of 10mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 to lesion 2).
Radiation: Radiation Therapy
7.5 Gy/Fraction for 3 days week 1 and 7.5 Gy/Fraction for 3 days week 7

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven breast cancer, metastatic (persistent or recurrent).
  • Failed ≥1 line of therapy (endocrine or chemotherapy) for metastatic disease.
  • Min. 3 distinct metastatic sites, at least one measurable lesion which is at least 1 cm or larger in largest diameter.
  • Must be ≥4 weeks since all of the following treatments (recovered from toxicity of prior treatment to ≤Grade 1, excluding alopecia):

    • major surgery;
    • radiotherapy;
    • chemotherapy (≥6 weeks since therapy if a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab);
    • immunotherapy;
    • biotherapy/targeted therapies.
  • >18 years of age.
  • Life expectancy >6 months.
  • Eastern Cooperative Oncology Group (ECOG) status 0 or 1.
  • Adequate organ function including:

    • Hemoglobin ≥10.0g/dL, absolute neutrophil count (ANC) ≥1,500/mm3, and platelets ≥100,000/mm3.
    • Hepatic: Serum total bilirubin ≤1.5x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if total bilirubin is ≤3.0mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2.5xULN. If patient has known liver metastases, ALT and/or AST ≤5xULN are allowed.
    • Renal: creatinine clearance ≥60mL/min.
    • Prothrombin (PT) and partial thromboplastin times (PTT) <ULN.
  • Negative for hepatitis viruses B and C unless consistent with prior vaccination or prior infection with full recovery.
  • Patients of childbearing potential must agree to use effective contraception while on study, and for ≥3 months after last treatment.
  • Understand and sign written informed consent document. No consent by durable power of attorney.

Exclusion Criteria:

  • Second malignancy - unless following curative intent therapy, has been disease free for ≥2 years with probability of recurrence <5%. Curatively treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are allowed.
  • Concurrent cancer therapy.
  • Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or disease that causes or threatens neurologic compromise (e.g. unstable vertebral metastases).
  • History of ascites or pleural effusions, unless successfully treated.
  • Organ transplant, including allogeneic bone marrow transplant.
  • Immunosuppressive therapy including:

    • Systemic corticosteroid therapy, including replacement therapy for hypoadrenalism. Inhaled or topical corticosteroids are allowed (if therapy is <5 days and is limited to systemic steroids as antiemetics);
    • Cyclosporine A, tacrolimus, or sirolimus.
  • Investigational agents within 4 weeks prior to study enrollment (≥6 weeks if treatment was long-acting agent such as monoclonal antibody).
  • Significant or uncontrolled medical illness, e.g. congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with remote history of asthma or active mild asthma may participate.
  • Active infection, including unexplained fever (>38.5°C).
  • Systemic autoimmune disease (e.g. systemic lupus erythematosus, active rheumatoid arthritis).
  • Known allergy to any component of GC1008.
  • Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or anti-coagulation therapy (including anti platelet agents i.e. aspirin, clopidogrel, ticlopidine, dipyridamole, other agents inducing long-acting platelet dysfunction). Patients with history of deep venous thrombosis are allowed if treated, completely resolved, and no treatment for >4months.
  • Calcium >11.0mg/dL (2.75mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g. bisphosphonates).
  • Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems, including, but not limited to:

    • Other serious non-malignancy-associated conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs;
    • Conditions, psychiatric, substance abuse, or other, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study;
  • Pregnant or nursing women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01401062

Contacts
Contact: Ravindran Kathirithamby 212 731-53335 Ravindran.Kathirithamby@nyumc.org

Locations
United States, California
David Geffen School of Medicine at UCLA Recruiting
Los Angeles, California, United States, 90095-1714
Contact: Vincent Basehart    310-794-0166    VBasehart@mednet.ucla.edu   
Principal Investigator: Percy Lee, M.D.         
United States, New York
New York University Langone Medical Center Cancer Center Recruiting
New York, New York, United States, 10016
Contact: Ravindran Kathirithamby    212-731-5335    Ravindran.Kathirithamby@nyumc.org   
Principal Investigator: Silvia C. Formenti, M.D.         
Sponsors and Collaborators
New York University School of Medicine
University of California, Los Angeles
Investigators
Principal Investigator: Silvia Formenti, M.D. New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01401062     History of Changes
Other Study ID Numbers: 11-00533, BC100481
Study First Received: July 20, 2011
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
metastatic breast cancer
TGF-beta
fresolimumab
monoclonal antibody
radiation therapy
abscopal response

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014