Fresolimumab and Radiotherapy in Metastatic Breast Cancer

NCT01401062 | Completed Phase 2 Results DMC

• 2 other identifiers: S11-00533BC100481
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

metastatic breast cancer; TGF-beta; fresolimumab; monoclonal antibody; radiation therapy; abscopal response

Outcome Measures

Primary Outcomes (1)

• Abscopal Response Rate

  Defined as the percentage of patients who have responses (complete or partial) outside the irradiated lesions. The abscopal response is assessed at 15 weeks, and confirmed minimum 4 weeks later. The abscopal response is evaluated based on immune-related response criteria (irRC) (Wolchok et al, 2009).

  up to 20 weeks

Study Arms (2)

Arm 1 (Fresolimumab 1 mg/kg)

EXPERIMENTAL

Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/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).

Drug: Fresolimumab; Radiation: Radiation Therapy

Arm 2 (Fresolimumab 10 mg/kg)

EXPERIMENTAL

Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/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).

Drug: Fresolimumab; Radiation: Radiation Therapy

Interventions

Fresolimumab DRUG

Also known as: GC1008

Arm 1 (Fresolimumab 1 mg/kg); Arm 2 (Fresolimumab 10 mg/kg)

Radiation Therapy RADIATION

Arm 1 (Fresolimumab 1 mg/kg); Arm 2 (Fresolimumab 10 mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• University of California, Los Angeles: collaborator

Study Sites (2)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-1714, United States

Location

New York University Langone Medical Center Cancer Center

New York, New York, 10016, United States

Location

Related Publications (3)

• Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

  PMID: 19934295 BACKGROUND

• Formenti SC, Hawtin RE, Dixit N, Evensen E, Lee P, Goldberg JD, Li X, Vanpouille-Box C, Schaue D, McBride WH, Demaria S. Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients. J Immunother Cancer. 2019 Jul 11;7(1):177. doi: 10.1186/s40425-019-0633-x.

  PMID: 31296256 DERIVED

• Sato M, Kadota M, Tang B, Yang HH, Yang YA, Shan M, Weng J, Welsh MA, Flanders KC, Nagano Y, Michalowski AM, Clifford RJ, Lee MP, Wakefield LM. An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-beta in human breast cancer. Breast Cancer Res. 2014 Jun 2;16(3):R57. doi: 10.1186/bcr3668.

  PMID: 24890385 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Camurati-Engelmann Syndrome

Interventions

fresolimumab; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Nelly Huppert
• Organization: NYU Langone Medical Center

Nelly.Huppert@nyumc.org

212-731-5003

Study Officials

• Silvia Formenti, M.D.

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 25, 2011
• Study Start: July 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: March 5, 2019
• Results First Posted: April 6, 2017

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)