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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Minas Gerais、ブラジル、30285-000
- Hospital da Baleia
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Porto Alegre、ブラジル、90610-000
- Hospital Sao Lucas da PUCRS
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Rio de Janeiro、ブラジル、20220-410
- Instituto Nacional de Cancer
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Sao Paulo、ブラジル、05651-901
- Hospital israelita Albert Einstein
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Sao Paulo、ブラジル、01308-050
- Hospital Sírio-Libanês
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Sao Paulo、ブラジル、01246-000
- Hospital das Clinicas FMUSP
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Sao Paulo、ブラジル、01401-904
- Hospital Alemao Oswaldo Cruz
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Rio Grande do Sul
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Porto Alegre、Rio Grande do Sul、ブラジル、90035-903
- Hospital de Clinicas de Porto Alegre
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:hu3S193
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20 mg/m2, intravenous, weekly for a maximum of 3 cycles (of 8 weeks each)
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Best Overall Response
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants With Adverse Events and Serious Adverse Events
時間枠: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%).
時間枠: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.
時間枠: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
時間枠: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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Clinical Benefit
時間枠: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)
時間枠: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
時間枠: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
時間枠: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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協力者と研究者
スポンサー
捜査官
- スタディチェア:Oren Smaletz, MD、Recepta Biopharma
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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