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HumanaH - Hu3s193 in the Treatment of Advanced Breast Cancer After Hormonal Therapy

Phase 2
Terminated
Conditions
Breast Cancer
Interventions
Biological: Hu3S193
Registration Number
NCT01370239
Lead Sponsor
Instituto do Cancer do Estado de São Paulo
Brief Summary

The humanized monoclonal antibody against Lewis Y antigen (Hu3S193) has been demonstrated to be safe in previous studies and has also been indicated as potential intervention in breast cancer. The study of this new agent in advanced breast cancer may contribute to the development of new strategies for patients that progressed after hormonal treatment.

Detailed Description

This is a national study, open label, single arm, phase II study which will be conducted in seven centers in Brazil. The study will be coordinated by the INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO in collaboration with RECEPTA Biopharma. The study is funded by the CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO (CNPq). Before any procedure relating to the study, patients must read and sign the informed consent (IC). The inclusion of patients begin immediately after regulatory approval and is expected to end after reaching the number of patients. The follow-up term will last at least 24 months for each patient included, unless limited by death, loss to follow up or withdrawal of informed consent. A total of 60 patients will be recruited in this study. The eligible patients must be 18 or older, confirmed diagnosis of breast cancer with locally advanced or metastatic progression after one or two lines of previous hormone treatment, confirmation of Lewis antigen expression -as assessed by central laboratory, measurable or evaluable disease and adequate organ function. Patients will receive weekly intravenous doses of the antibody Hu3S193 until disease progression, unacceptable toxicity, withdrawal of consent or the investigator's decision, whichever occurs first. The study's primary endpoint is the clinical benefit rate.

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
23
Inclusion Criteria
  • Diagnosis of breast cancer with locally advanced or metastatic (stages IIIB, IIIC or IV according to TNM classification), confirmed histologically with no intention to curative treatment by radiotherapy or surgery;
  • Clinical or radiological progression after one or two lines of previous hormone treatment, including adjuvant treatment;
  • Positive for ER and / or PR expression documented by IHC;
  • Confirmed expression of Lewis Y antigen by IHC;
  • Presenting the performance status of 0 or 1 according to Eastern Cooperative Oncology Group (ECOG);
  • Have a measurable or evaluable disease by Response of Evaluation Criteria in Solid Tumors (RECIST);
  • Adequate organ function, assessed by laboratory tests obtained at least 2 weeks before the first day of treatment and within the following parameters:

absolute neutrophil count ≥ 1.5 x 109 / L; platelet count ≥ 100 x 109 / L; serum bilirubin ≤ 2.0 mg / dL; AST/ALT ≤ 2.5 x upper limit of normal; serum creatinine ≤ 2.0 mg / dL;

  • Expected survival > 12 weeks;
  • In patients with childbearing potential: Negative pregnancy confirmed by test done 21 days before the date of study treatment initiation;
  • Willingness and ability to comply with the protocol for the duration of the study.
Exclusion Criteria
  • Patients subjected previously to more than two lines of hormonal therapy, including adjuvant treatment;
  • Presenting the amplification or overexpression of HER-2;
  • Systemic corticosteroids or immunosuppressive agents used concomitantly with the study or have used systemic corticosteroids or immunosuppressants in the last 14 days before the first dose of the investigational drug;
  • Visceral metastatic disease with life-threatening (as defined by extensive liver involvement), or symptomatic pulmonary lymphangitic carcinomatosis or any degree of cerebral or leptomeningeal involvement;
  • Previous or current history of clinically significant cardiac disease (class III or IV according to New York Heart Association);
  • Clinically significant arrhythmia;
  • History of myocardial infarction within the last 6 months;
  • Previous or current history of other severe diseases (eg, severe ascites requiring repeated drainage, active infections requiring antibiotics, bleeding, inflammatory bowel disease or chronic diseases that may interfere with obtaining accurate results of the study);
  • Previous chemotherapy for metastatic disease (adjuvant chemotherapy is acceptable, if more than four weeks between its completion and inclusion in the study;
  • Radiotherapy within 4 weeks before inclusion in the study or with no recovery from the toxic effects of radiotherapy when done up to 6 weeks before inclusion in the study, except for palliative radiotherapy for bone metastases involving <25 % bone marrow;
  • Treatment with biological agents, immunotherapy or surgery within 4 weeks before inclusion in the study or with no recovery from the toxic effects of these treatments when made until six weeks prior to study entry (prior treatment with bisphosphonates is allowed, it can be continued after inclusion in the study);
  • Any investigational agent treatment within 12 months prior to study entry, unless the investigator considers that the participation in the study may benefit the patient;
  • Previous or current history of another type of tumor, excluding skin cancer, melanoma, in situ cervix carcinoma or in situ ductal carcinoma or lobular breast if properly treated;
  • Uncontrolled hypercalcemia (defined as total calcium> 11.5 mg / dL)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Hu3S193Hu3S193Single arm
Primary Outcome Measures
NameTimeMethod
Complete response, partial response or stable disease.more than 24 weeks

The primary efficacy analysis will be done through the clinical benefit rate, as defined by the proportion of patients achieving best response, complete response, partial response or stable disease for more than 24 weeks

Secondary Outcome Measures
NameTimeMethod
Overall survival24 weeks after patient discontinuation (at minimum) or until death

until death

Response rate24 weeks after patient discontinuation (at minimum)

from inclusion until disease progression or death

Progression free survivaluntil disease progression or 24 weeks after patient discontinuation (at minimum)

Evaluated radiologically by CT

Non progression rate24 weeks after patient discontinuation (at minimum)

From patient inclusion until disease progression or death - evaluated radiologically by CT

Assessment of any sign, symptom or undesirable medical condition that occurs after the first administration of the investigational agentUntil disease progression or 30 days after patient discontinuation

Trial Locations

Locations (7)

Universidade Federal de Goias

🇧🇷

Goias, Brazil

Instituto Do Câncer Do Estado de São Paulo

🇧🇷

Sao Paulo, Brazil

Hospital Sirio Libanes

🇧🇷

Sao Paulo, Brazil

Universidade Federal Do Ceará

🇧🇷

Fortaleza, Ceará, Brazil

Instituto Nacional Do Câncer

🇧🇷

Rio de Janeiro, Brazil

PONTIFíCIA UNIVERSIDADE CATÓLICA DO RIO GRANDE DO SUL

🇧🇷

Porto Alegre, RIO Grande DO SUL, Brazil

Hospital Do Câncer de Barretos

🇧🇷

Barretos, SÃO Paulo, Brazil

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