Clinical trial NCT01137071: Consolidation Therapy With Hu3S193 for Women With Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Lead sponsor: Recepta Biopharma
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 1-year PFS2 Rate After the Beginning of Rescue Platinum-based Chemotherapy
timeFrame: 1-Year - From platinum-based rescue chemotherapy start date until documented disease progression or death of any cause whichever occurred first.
Secondary outcomes:
measure: 1-year Disease Progression-free Survival Rate
timeFrame: 1 year from the beginning of platinum-based rescue chemotherapy start date
measure: Two-year Overall Survival Rate
timeFrame: 2-year overall survival rate after the beginning of rescue platinum-based chemotherapy.
measure: Safety - Vital Signs - Heart Rate
timeFrame: Baseline, week 2 , week 4 and week 27
measure: Safety - Vital Signs - Respiratory Rate
timeFrame: Baseline, week 2, week 4 and week 27
measure: Safety - Vital Signs - Systolic and Diastolic Blood Pressure
timeFrame: Baseline, week 2, week 4 and week 27
measure: Safety - Vital Signs - Temperature
timeFrame: Baseline, week 2, week 4 and week 27
measure: Incidence of Adverse Events (AEs) - Gastrointestinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Immune System Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Nervous System Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Investigations
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Respiratory, Thoracic and Mediastinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Infections and Infestations; Gastrointestinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Blood and Lymphatic System Disorders (Anaemia)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Psychiatric Disorders (Anxiety)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Vascular Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Cardiac Disorders; General Disorders and Administration Site Conditions; Respiratory, Thoracic and Mediastinal Disorders (Chest Pain)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Musculoskeletal and Connective Tissue Disorders (Chills)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Ear and Labyrinth Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Hepatobiliary Disorders; Injury, Poisoning and Procedural Complications (Hepatotoxicity)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Immune System Disorders; General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Infusion Related Reaction)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Immune System Disorders; Respiratory, Thoracic and Mediastinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; General Disorders and Administration Site Conditions; Nervous System Disorders (Spinal Pain)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; Injury, Poisoning and Procedural Complications
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Psychiatric Disorders (Depression)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Renal and Urinary Disorders (Dysuria)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Renal and Urinary Disorders; Infections and Infestations (Urinary Tract Infection)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Reproductive System and Breast Disorders (Vulvovaginal Dryness)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Respiratory, Thoracic and Mediastinal Disorders; Cardiac Disorders (Dyspnoea)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Injury, Poisoning and Procedural Complications
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Cardiac Disorders; Vascular Disorders; Nervous System Disorders (Dizziness)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Ear and Labyrinth Disorders; Nervous System Disorders (Vertigo)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Endocrine Disorders; Metabolism and Nutrition Disorders (Hyperglycaemia)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Eye Disorders (Ocular Hyperaemia)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders (Pharyngitis)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Reproductive System and Breast Disorders; Renal and Urinary Disorders (Pelvic Pain)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Gastrointestinal Disorders; Vascular Disorders (Anal Haemorrhage)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Hyperthermia)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - General Disorders and Administration Site Conditions; Injury, Poisoning and Procedural Complications (Catheter Site Inflammation)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Immune System Disorders; Blood and Lymphatic System Disorders; Injury, Poisoning and Procedural Complications (Transfusion Reaction)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Infections and Infestations; Respiratory, Thoracic and Mediastinal Disorders (Bronchitis)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Infections and Infestations; Renal and Urinary Disorders (Urinary Tract Infection Bacterial)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Investigations (Blood Cholesterol Increased)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Musculoskeletal and Connective Tissue Disorders; General Disorders and Administration Site Conditions; Renal and Urinary Disorders (Flank Pain)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Nervous System Disorders; Psychiatric Disorders; Respiratory, Thoracic and Mediastinal Disorders (Hoarseness)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Psychiatric Disorders; Nervous System Disorders (Insomnia)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Infections and Infestations (Tinea Pedis)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Skin and Subcutaneous Tissue Disorders; Reproductive System and Breast Disorders (Vulvovaginal Pruritus)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Vascular Disorders; Gastrointestinal Disorders (Haemorrhoids)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Adverse Events (AEs) - Vascular Disorders; Respiratory, Thoracic and Mediastinal Disorders (Epistaxis)
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Serious Adverse Events (SAEs) - Gastrointestinal Disorders
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Incidence of Serious Adverse Events (SAEs) - Musculoskeletal and Connective Tissue Disorders - Hip Fracture
timeFrame: From the first infusion of medication to 30 days after the last one
measure: Overall Mean Pharmacokinetic (PK) Data (Minimum and Maximum Concentrations)
timeFrame: Predose and Postdose on weeks 1, 2, 3, 4, 5, 7 and 9
measure: Two-year Overall Survival: Median Time to Death
timeFrame: 2-year overall survival rate after the beginning of rescue platinum-based chemotherapy.
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Núcleo de Oncologia da Bahia
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Cetus Hospital-Dia Oncologia Ltda - Filial Belo Horizonte
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande do Sul
city: Barretos
country: Brazil
facility: Hospital de Câncer de Barretos
state: São Paulo
city: Jaú
country: Brazil
facility: Fundação Amaral Carvalho
state: São Paulo
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo "Octávio Frias de Oliveira"
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
Study officials:
affiliation: Recepta Biopharma S.A.
name: Oren Smaletz, MD
role: STUDY_CHAIR
References:
citation: Smaletz O, Ismael G, Del Pilar Estevez-Diz M, Nascimento ILO, de Morais ALG, Cunha-Junior GF, Azevedo SJ, Alves VA, Moro AM, Yeda FP, Dos Santos ML, Majumder I, Hoffman EW. Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission. Int J Gynecol Cancer. 2021 Apr;31(4):562-568. doi: 10.1136/ijgc-2020-002239. Epub 2021 Mar 4.