- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00617773
Hu3S193 in Treating Women With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
A PHASE II TRIAL OF Hu3S193 THERAPY FOR PATIENTS WITH PLATINUM REFRACTORY OR PLATINUM RESISTANT EPITHELIAL OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER
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 in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cavity cancer.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
Primary
- To evaluate the efficacy of monoclonal antibody Hu3S193 in women with platinum-resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer, based on RECIST criteria (Response Evaluation Criteria in Solid Tumors).
Secondary
- To determine the safety of the study drug.
- To determine the drug pharmacokinetics when administered in multiple weekly injections.
Exploratory analysis
- Clinical Benefit (objective response rate + tumor stabilization).
- Progression Free Survival (PFS).
- Duration of Response.
- Overall Survival.
- 12-month survival rate.
OUTLINE: This is a multicenter study.
Patients receive monoclonal antibody Hu3S193 IV over 1 hour once weekly in weeks 1-8. Treatment repeats every 8 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed monthly.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Minas Gerais, Brasilien, 30285-000
- Hospital da Baleia
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Porto Alegre, Brasilien, 90610-000
- Hospital Sao Lucas da PUCRS
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Rio de Janeiro, Brasilien, 20220-410
- Instituto Nacional de Câncer
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Sao Paulo, Brasilien, 05651-901
- Hospital Israelita Albert Einstein
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Sao Paulo, Brasilien, 01308-050
- Hospital Sirio-Libanes
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Sao Paulo, Brasilien, 01246-000
- Hospital das Clinicas FMUSP
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Sao Paulo, Brasilien, 01401-904
- Hospital Alemao Oswaldo Cruz
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brasilien, 90035-903
- Hospital de Clinicas de Porto Alegre
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
DISEASE CHARACTERISTICS:
Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma
- Progressive disease
- Disease must express Lewis-Y antigen documented by immunohistochemistry in archived or fresh primary or metastatic tumor biopsies
Measurable disease, including at least one measurable lesion, according to RECIST criteria or CA-125 (Cancer Antigen-125) > 2 times upper normal limit
- Pleural effusion, ascites, bone metastases, and lesions located in previously irradiated areas are not considered measurable
Disease must be considered platinum-refractory or resistant, meeting any of the following criteria:
- Platinum-refractory defined as progression during the initial platinum-based chemotherapy regimen or failure to achieve a complete response (e.g., stable disease or partial response) with evidence of progressive disease (by physical examination, radiological exams, or CA-125) during the initial platinum-based chemotherapy
- Platinum-resistant defined as recurrence within six months of completion of the initial platinum-based regimen (primary platinum-resistance) or recurrence after six months of completion of the initial platinum-based regimen (still considered platinum-sensitive, but incurable by any approach, that will progress to a secondary platinum-resistance scenario) and failure to ≥ 1 re-induction with a platinum-based regimen (secondary platinum-resistance)
- No high tumor burden, as assessed by the investigator
- No rapidly progressing disease, as assessed by clinical evaluation
- No known CNS (Central Nervous System) involvement by tumor
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status > 70%
- Life expectancy ≥ 12 weeks
- ANC (absolute neutrophil count) ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum bilirubin ≤ 2.0 mg/dL
- AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if with liver metastases)
- Creatinine ≤ 2.0 mg/dL
- Prothrombin time < 1.3 times control
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- NYHA (New York Heart Association) class III or IV heart disease
- Clinically significant arrhythmias by ECG
- Myocardial infarction within the past 6 months
Any other serious illness, including any of the following:
- Severe ascites
- Severe active infections requiring antibiotics
- Bleeding disorders
- Chronic inflammatory bowel disease
- Diseases that might interfere with the collection of accurate results from this study
- Positive for human anti-human antibodies
- Prior history of tumor (excluding adequately treated nonmelanoma skin cancer or carcinoma in situ of the uterine cervix)
- Uncontrolled hypercalcemia (i.e., > 11.5 mg/dL)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from the toxic effects of any prior therapy
- No concurrent systemic steroids or immunosuppressant agents
No more than 1 prior non-platinum-containing regimen for the treatment of platinum-resistant/refractory disease
- Patients who receive 2 or more different non-platinum-containing chemotherapy regimens for platinum-resistant/refractory disease are not eligible
- More than 4 weeks since prior and no other concurrent chemotherapy, radiotherapy, radiopharmaceuticals (e.g., ^32P), biological therapy, anti-estrogen therapy (including tamoxifen), immunotherapy, or surgery
- More than12 weeks since prior investigational agent
- No prior treatment with a murine or humanized antibody and/or antibody fragment
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: hu3S193
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20 mg/m2, intravenous, weekly for a maximum of 3 cycles (of 8 weeks each)
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Best Overall Response
Tidsramme: From start of study treatment until the end of Cycle 1 (8 weeks), Cycle 2 (16 weeks) or Cycle 3 (24 weeks).
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Best response recorded from the start of treatment until disease progression/recurrence. Includes all patients evaluable for efficacy, regardless of used criteria: RECIST or CA-125 (Cancer Antigen 125). Evaluation of target lesions: Complete Response (CR), resolution of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD sum) of target lesions, taking as reference the baseline LD sum; Progressive Disease (PD), a 20% increase in LD sum of target lesions or the appearance of new lesion(s); Stable Disease (SD), no sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Evaluation of non-target lesions: CR, resolution of all non-target lesions and normalization of CA-125 level; SD, persistence of one or more non-target lesions and/or maintenance of CA-125 level above the normal limits; PD, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
From start of study treatment until the end of Cycle 1 (8 weeks), Cycle 2 (16 weeks) or Cycle 3 (24 weeks).
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Adverse Events and Serious Adverse Events
Tidsramme: From the first dose of investigational product up to 30 days after the last dose of investigational product
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A listing of all adverse events is located in the Reported Adverse Event module.
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From the first dose of investigational product up to 30 days after the last dose of investigational product
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Number of Participants With Adverse Events Reasonably Related to the Investigational Product (Incidence Greater Than 5%).
Tidsramme: From the first dose of investigational product up to 30 days after the last dose of investigational product
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Adverse events with possible, probable or definite relationship to the investigational product were considered to be reasonably related.
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From the first dose of investigational product up to 30 days after the last dose of investigational product
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Mean Cmax and Cmin of Hu3S193 Relating to the First 4 Doses.
Tidsramme: Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, and 4 of Cycle 1.
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Cmax = Peak (post-dosing) IP (Investigational Product) plasma concentration.
Cmin = Trough (pre-dosing) IP plasma concentration (Cmin).
Plasma concentration of Hu3S193 expressed in µg/mL.
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Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, and 4 of Cycle 1.
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Mean Cmax and Cmin of Hu3S193 Relating to the First 8 Doses
Tidsramme: Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, 4, 5, 6, 7 and 8 of Cycle 1.
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Cmax = Peak (post-dosing) IP plasma concentration.
Cmin = Trough (pre-dosing) IP plasma concentration (Cmin).
Plasma concentration of Hu3S193 expressed in µg/mL.
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Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, 4, 5, 6, 7 and 8 of Cycle 1.
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Clinical Benefit
Tidsramme: From start of study treatment until the end of Cycle 3 (24 weeks).
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The clinical benefit was calculated considering all patients with objective response rate (CR + PR) or stable disease (SD) for at least 24 weeks according RECIST or CA-125 if patients were non-assessable or when assessment by RECIST was unknown. Clinical benefit = 100% x (Number of patients with objective response + Number of patients with stable disease for at least 24 weeks) / Number of patients included in the efficacy population. The evaluation of target and non-target lesions is described at the Outcome Measure titled "Best Overall Response". CR: Complete Response; PR: Partial Response; SD: Stable Disease. |
From start of study treatment until the end of Cycle 3 (24 weeks).
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Progression Free Survival (PFS)
Tidsramme: From the first day of the investigational product administration until documentation of disease progression or death due to any cause (whichever occurred first). An average of 16.5549 weeks.
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Progression free survival (PFS) is defined as the duration of time from start of treatment to time of disease progression.
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From the first day of the investigational product administration until documentation of disease progression or death due to any cause (whichever occurred first). An average of 16.5549 weeks.
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Overall Survival
Tidsramme: From start of study treatment until death or the date that patients were last known to be alive. An average of 56.126 weeks.
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Measured from the beginning of therapy until the date of death or for patients without a known date of death, they will be censored at the date they were last known to be alive.
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From start of study treatment until death or the date that patients were last known to be alive. An average of 56.126 weeks.
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12-Month Survival Rate
Tidsramme: 12 months from the start of study treatment.
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Rate of patients alive 12 months after starting therapy with the investigational product.
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12 months from the start of study treatment.
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studiestol: Oren Smaletz, MD, Recepta Biopharma
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- RCPOv01-06
- RCP-Ov-01.06 (Anden identifikator: Recepta Biopharma)
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Kliniske forsøg med Livmoderhalskræft
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National Cancer Institute (NCI)Ikke rekrutterer endnuRecidiverende platinfølsomt tuba fallopii højgradigt serøst adenokarcinom | Recidiverende Platinfølsom Ovarie Højgradigt Serøs Adenokarcinom | Recurrent Platinum-Sensitive Primary Peritoneal High Grade Serous Adenocarcinoma | Recurrent Platinum-Sensitive Endometrioid Adenokarcinom i Æggelederen og andre forhold
Kliniske forsøg med hu3S193
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Ludwig Institute for Cancer ResearchNational Cancer Institute (NCI)AfsluttetLivmoderhalskræftForenede Stater
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Ludwig Institute for Cancer ResearchNational Cancer Institute (NCI)AfsluttetRadioaktivt mærket monoklonalt antistof til behandling af patienter med avanceret ovarieepitelcancerLivmoderhalskræftForenede Stater
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Ludwig Institute for Cancer ResearchNational Cancer Institute (NCI)AfsluttetLungekræftForenede Stater
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Recepta BiopharmaAfsluttetLivmoderhalskræft | Æggelederkræft | Peritoneal hulrumskræftBrasilien
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Ludwig Institute for Cancer ResearchAfsluttetKolorektal cancerForenede Stater