Consolidation Therapy With Hu3S193 for Women With Ovarian, Primary Peritoneal or Fallopian Tube Cancer

A Phase II Trial of Hu3S193 Consolidation Therapy for Patients With Relapsing Platinum-sensitive Ovarian, Primary Peritoneal and Fallopian Tubes Adenocarcinoma, Who Achieved a Second Complete Response

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01137071

Enrollment

Registered

2010-06-04

Start date

2011-04-30

Completion date

2015-06-30

Last updated

2017-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Brief summary

RATIONALE: Monoclonal antibodies, such as Hu3S193, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well Hu3S193 works as a consolidation therapy for women with relapsing platinum-sensitive ovarian, primary peritoneal or fallopian tube cancer.

Detailed description

This is a phase II multicenter trial with Hu3S193 as a single agent in a consolidation strategy in patients with relapsing platinum-sensitive ovarian, primary peritoneal and fallopian tubes cancer who achieve a second Complete Response after a platinum-based chemotherapy after platinum-based chemotherapeutical regimen. Fifty-one (51) patients with relapsing platinum-sensitive ovarian, primary peritoneal or fallopian tubes adenocarcinoma will receive doses of 30 mg/m2 of Hu3S193 as a single agent every two weeks, in a total of 12 doses (treatment period duration: 23 weeks). After the treatment period, patients will be evaluated every 3 months for the first two years, and every 6 months for more 3 years, and then in an annual-basis until disease progression or death, whichever happens first.

Interventions

BIOLOGICALMonoclonal antibody Hu3S193

30 mg/m2 of Monoclonal antibody Hu3S193, IV as a single agent every two weeks, in a total of 12 doses (treatment period duration: 23 weeks). Anti-Lewis Y humanized monoclonal antibody designated orphan drug by the FDA on March 09, 2012 for the treatment of ovarian cancer, not yet approved for the orphan designation.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. The Informed Consent Form (ICF) must be signed before the performance of any study specific procedure or treatment. 2. Female patients of \>= 18 years of age. 3. Relapsing ovarian adenocarcinoma, fallopian tubes or primary peritoneal who achieved a complete clinical response after the first treatment of relapse with platinum-based regimen. A complete response is defined as the absence of cancer related symptoms, normal physical exam, normal CA-125 (tumor marker) level, normal chest X-ray and CT-scan of abdomen/pelvis. Eligibility allows the presence of nonspecific findings as long as not showing clear evidence of disease such as: lymph node and/or soft tissue abnormalities \<= 1.0 cm which are frequently present on the pelvis and will not be considered to be a conclusive evidence of disease. 4. Expression of antigen Ley documented by immunohistochemistry of archived primary or metastatic tumor samples. 5. The patient must have been submitted at least to hysterectomy and bilateral salpingo-oophorectomy before entering the study and must have received platinum-based chemotherapy as adjunctive or neo-adjunctive treatment at the first presentation. 6. At least 5 and no more than 8 cycles of platinum combination therapy (i.e. doublet) as treatment for the first relapse. 7. All side effects from chemotherapy must have been resolved or must be grade 1. 8. Interval between the last dose of the treatment with platinum that achieved clinical CR (complete response) and the first dose of Hu3S193 =\< 8 weeks. 9. Karnofsky performance status \>= 70%. 10. Results of laboratorial exams in the first 2 weeks before drug infusion within the following values: * Absolute Neutrophil Count \>= 1.5 x 10x3 / mm3 * Platelet count \>= 100 x 10x3 / mm3 * Blood bilirubin \<= 2.0 mg/dL * Aspartate aminotransaminase (AST) and Alanine aminotransferase (ALT) \<= 2.5 x upper limit of normal (ULN). * Blood creatinine \<= 2.0 mg/dL. * Prothrombin time \< 1.3 x control 11. Expected survival \>= 12 months. 12. Patients must be willing to participate and be able to comply with the protocol throughout the study.

Exclusion criteria

1. Mucinous or clear cell histology. 2. Patients must not have received Bevacizumab as part of their treatment on relapse. 3. Diagnosis of primary tumor relapse made exclusively based on elevated levels of serum CA-125 with values \<2-fold the upper limit of normality. 4. Concomitant use of systemic corticosteroids or immunosuppressive agents. 5. Known CNS (central nervous system) involvement by tumor. 6. Clinically significant heart disease (New York Heart Association Class III or IV). 7. ECG indicating clinically significant arrhythmia. 8. History of myocardial infarction within 6 months. 9. Other serious diseases, (e.g.: serious infections requiring antibiotics, bleeding disorders, chronic inflammatory bowel disease, or diseases that may interfere in the obtainment of accurate study results). 10. Radiotherapy treatment, radiopharmaceuticals (e.g. 32P), biological therapy, anti-estrogen therapy (including tamoxifen), immunotherapy or surgery within 4 weeks before the first administration of investigational product fail to recover from toxic effects of any of these therapies within 6 weeks prior to study inclusion. 11. Exposure to any investigational product within 4 months prior to study inclusion. 12. Previous treatment with a humanized murine antibody and/or fragment of such antibody. 13. Previous history of tumor (excluding appropriately treated non-melanoma skin cancer or carcinoma in situ of the cervix or no evidence of disease within at least 5 years for previous breast cancer or stage I endometrial cancer).

Design outcomes

Primary

Measure	Time frame	Description
1-year PFS2 Rate After the Beginning of Rescue Platinum-based Chemotherapy	1-Year - From platinum-based rescue chemotherapy start date until documented disease progression or death of any cause whichever occurred first.	PFS2 is defined by the interval from the beginning of rescue platinum-based chemotherapy until documented disease progression or death for any cause while the patient was under study or during the prolonged follow-up period. Disease progression is defined by appearance of any new lesion (measurable and non-measurable) by the RECIST criteria. Disease progression date is the date when a new lesion is documented.

Secondary

Measure	Time frame	Description
Two-year Overall Survival Rate	2-year overall survival rate after the beginning of rescue platinum-based chemotherapy.	Overall survival was calculated as the time interval between the date of beginning of rescue platinum-based chemotherapy and date of death for any cause.
Safety - Vital Signs - Heart Rate	Baseline, week 2 , week 4 and week 27	Vital signs were assessed throughout the study treatment (consolidation therapy).Through study completion, an average of 27 weeks.
Safety - Vital Signs - Respiratory Rate	Baseline, week 2, week 4 and week 27	Vital signs during the study treatment (consolidation therapy). Through study completion, an average of 27 weeks.
Safety - Vital Signs - Systolic and Diastolic Blood Pressure	Baseline, week 2, week 4 and week 27	Both parameters were assessed throughout the study treatment. Vital signs during the study treatment (consolidation therapy). Through study completion, an average of 27 weeks.
Safety - Vital Signs - Temperature	Baseline, week 2, week 4 and week 27	Vital signs during the study treatment (consolidation therapy). Through study completion, an average of 27 weeks.
Incidence of Adverse Events (AEs) - Gastrointestinal Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Immune System Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Nervous System Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Investigations	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Respiratory, Thoracic and Mediastinal Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Infections and Infestations; Gastrointestinal Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Blood and Lymphatic System Disorders (Anaemia)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Psychiatric Disorders (Anxiety)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Vascular Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Cardiac Disorders; General Disorders and Administration Site Conditions; Respiratory, Thoracic and Mediastinal Disorders (Chest Pain)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Musculoskeletal and Connective Tissue Disorders (Chills)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Ear and Labyrinth Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Hepatobiliary Disorders; Injury, Poisoning and Procedural Complications (Hepatotoxicity)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Immune System Disorders; General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Infusion Related Reaction)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Immune System Disorders; Respiratory, Thoracic and Mediastinal Disorders	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; General Disorders and Administration Site Conditions; Nervous System Disorders (Spinal Pain)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; Injury, Poisoning and Procedural Complications	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Psychiatric Disorders (Depression)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Renal and Urinary Disorders (Dysuria)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Renal and Urinary Disorders; Infections and Infestations (Urinary Tract Infection)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Reproductive System and Breast Disorders (Vulvovaginal Dryness)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Respiratory, Thoracic and Mediastinal Disorders; Cardiac Disorders (Dyspnoea)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Injury, Poisoning and Procedural Complications	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Cardiac Disorders; Vascular Disorders; Nervous System Disorders (Dizziness)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Ear and Labyrinth Disorders; Nervous System Disorders (Vertigo)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Endocrine Disorders; Metabolism and Nutrition Disorders (Hyperglycaemia)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Eye Disorders (Ocular Hyperaemia)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Two-year Overall Survival: Median Time to Death	2-year overall survival rate after the beginning of rescue platinum-based chemotherapy.	Overall survival was calculated as the time interval between the date of beginning of rescue platinum-based chemotherapy and date of death for any cause.
Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders (Pharyngitis)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Reproductive System and Breast Disorders; Renal and Urinary Disorders (Pelvic Pain)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Vascular Disorders (Anal Haemorrhage)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Hyperthermia)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Catheter Site Inflammation)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Immune System Disorders; Blood and Lymphatic System Disorders; Injury, Poisoning and Procedural Complications (Transfusion Reaction)	From the first infusion of medication to 30 days after the last one	The incidence of adverse events (percentage of patients with at least one adverse event and serious adverse events (overall and with reasonable relationship)) was assessed for the safety population
Incidence of Adverse Events (AEs) - Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders (Bronchitis)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Infections and Infestations; Renal and Urinary Disorders (Urinary Tract Infection Bacterial)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Investigations (Blood Cholesterol Increased)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; General Disorders and Administration Site Conditions; Renal and Urinary Disorders (Flank Pain)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Nervous System Disorders; Psychiatric Disorders; Respiratory, Thoracic and Mediastinal Disorders (Hoarseness)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Psychiatric Disorders; Nervous System Disorders (Insomnia)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
1-year Disease Progression-free Survival Rate	1 year from the beginning of platinum-based rescue chemotherapy start date	—
Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Reproductive System and Breast Disorders (Vulvovaginal Pruritus)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Vascular Disorders; Gastrointestinal Disorders (Haemorrhoids)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Adverse Events (AEs) - Vascular Disorders; Respiratory, Thoracic and Mediastinal Disorders (Epistaxis)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.
Incidence of Serious Adverse Events (SAEs) - Gastrointestinal Disorders	From the first infusion of medication to 30 days after the last one	A SAE was defined as an AE that met one of the following conditions: Death during the protocol-defined surveillance period; Potentially fatal event (defined as a patient at immediate risk of death at the time of the event); An event requiring the patient's hospitalization or prolongation of an existing hospitalization during the protocol-defined surveillance period; An event resulting in congenital anomaly or birth defect; An event resulting in a persistent or significant disability/incapacity; Any other major medical event that did not result in death, was not life threatening, or did not require hospitalization, but that could be considered a SAE when, based on the appropriate medical judgment, it presented a risk for the patient and required medical or surgical intervention to prevent one of the outcomes listed above.
Incidence of Serious Adverse Events (SAEs) - Musculoskeletal and Connective Tissue Disorders - Hip Fracture	From the first infusion of medication to 30 days after the last one	A SAE was defined as an AE that met one of the following conditions: Death during the protocol-defined surveillance period; Potentially fatal event (defined as a patient at immediate risk of death at the time of the event); An event requiring the patient's hospitalization or prolongation of an existing hospitalization during the protocol-defined surveillance period; An event resulting in congenital anomaly or birth defect; An event resulting in a persistent or significant disability/incapacity; Any other major medical event that did not result in death, was not life threatening, or did not require hospitalization, but that could be considered a SAE when, based on the appropriate medical judgment, it presented a risk for the patient and required medical or surgical intervention to prevent one of the outcomes listed above.
Overall Mean Pharmacokinetic (PK) Data (Minimum and Maximum Concentrations)	Predose and Postdose on weeks 1, 2, 3, 4, 5, 7 and 9	Cmax = Peak (postdosing) Hu3S193 plasma concentration. Cmin = Trough (predosing) Hu3S193 plasma concentration (Cmin). Plasma concentration of Hu3S193 expressed in μg/mL.
Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Infections and Infestations (Tinea Pedis)	From the first infusion of medication to 30 days after the last one	The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.

Countries

Brazil

Participant flow

Recruitment details

This was a Brazilian, multicentric clinical trial. From April 12, 2011 to October 31, 2013 a total of 37 patients were screened for this study, of whom 29 received at least one dose of the investigational product and 07 were considered noneligible.

Pre-assignment details

Patients were considered included in the study on the day of the first investigational product administration after investigator assured that patients met all the inclusion criterions and none of the exclusion criterions.

Participants by arm

Arm	Count
Monoclonal Antibody hu3S193 hu3S193: 30mg/m2, intravenous, every other week (total of 12 infusions) for a total of 23 weeks	29
Total	29

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Disease Progression	11
Overall Study	Withdrawal by Subject	2
Overall Study	Wrongly Included	1

Baseline characteristics

Characteristic	Monoclonal Antibody hu3S193
Age, Continuous	55.69 Years
Gender Female	29 Participants
Gender Male	0 Participants
Race/Ethnicity, Customized Black	1 participants
Race/Ethnicity, Customized Brown	4 participants
Race/Ethnicity, Customized Other	0 participants
Race/Ethnicity, Customized White	24 participants
Race/Ethnicity, Customized Yellow	0 participants
Region of Enrollment Brazil	29 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	28 / 29
serious Total, serious adverse events	3 / 29

Outcome results

Primary

1-year PFS2 Rate After the Beginning of Rescue Platinum-based Chemotherapy

PFS2 is defined by the interval from the beginning of rescue platinum-based chemotherapy until documented disease progression or death for any cause while the patient was under study or during the prolonged follow-up period. Disease progression is defined by appearance of any new lesion (measurable and non-measurable) by the RECIST criteria. Disease progression date is the date when a new lesion is documented.

Time frame: 1-Year - From platinum-based rescue chemotherapy start date until documented disease progression or death of any cause whichever occurred first.

Population: In the ITT (intention to treat) population, 25 patients out of the 29 considered for the PFS2 analysis presented disease progression or death and 4 were censored. The median time to disease progression or death was 11.8 months (95% CI (confidence interval), 10.6 to 13.9 months).

Arm	Measure	Value (MEDIAN)
hu3S193	1-year PFS2 Rate After the Beginning of Rescue Platinum-based Chemotherapy	11.7614 Months

Secondary

1-year Disease Progression-free Survival Rate

Time frame: 1 year from the beginning of platinum-based rescue chemotherapy start date

Population: In the ITT (Intention-to-treat) population, 25 patients out of the 29 considered for the PFS2 analysis presented disease progression or death and 4 were censored.

Arm	Measure	Value (NUMBER)
hu3S193	1-year Disease Progression-free Survival Rate	48.2 percentage of participants

Secondary

Incidence of Adverse Events (AEs) - Blood and Lymphatic System Disorders (Anaemia)

The Good Clinical Practice Guidelines define an Adverse Event as any untoward medical event that occurs in a patient or study patient receiving a pharmaceutical product, regardless of its causal relationship with the study treatment. Accordingly, an AE was considered as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or aggravated) temporally associated with the use of an investigational product.

Time frame: From the first infusion of medication to 30 days after the last one