A Phase II Study of Paclitaxel and Carboplatin in Patients With an Elevated-Risk Cancer of the Uterus
A Phase II Study of Paclitaxel and Carboplatin in Patients With Intermediate-Risk Adenocarcinoma of the Endometrium
調査の概要
詳細な説明
Endometrial cancer is the most common gynecologic malignancy in the United States with 40,880 new cases diagnosed and 7,310 deaths attributable to this malignancy expected in 2005. The majority of patients diagnosed with endometrial cancer have early stage disease that is amenable to treatment with hysterectomy and bilateral salpingo-oophorectomy with excellent clinical outcomes. Surgical staging has improved accuracy over clinical staging for defining a low-risk population of patients who have favorable long-term outcomes with surgery alone. However, approximately 10-15% of patients with surgical stage I endometrial carcinoma (confined to the uterus) will have invasion to the outer one-half of the myometrium (stage IC) and a moderately to poorly differentiated tumor (grade 2 or 3). These patients are at a higher risk for recurrence (approximately 20-25% recurrence rate over 5 years). This patient population has been historically considered at "intermediate-risk" for recurrence because they are at lower risk than patient with disease spread beyond the uterus, but higher risk than patients with a grade 1 tumor or minimally invasive (Stage IA or IB). The optimal mode of postoperative management for this population of patients has yet to be defined.
Historically, radiation therapy has been used in some form in patients diagnosed with intermediate-risk endometrial cancer. Two randomized trials published in the last 5 years have evaluated the use of adjuvant radiation therapy in patients with intermediate-risk endometrial adenocarcinoma. the Gynecologic Oncology Group (GOG) studied the use of adjuvant whole pelvic radiation (WPRT) versus no adjuvant therapy (NAT) in patients with stage IB, IC, and II (occult)endometrial adenocarcinoma. In a study of 392 patients, the use of WPRT had a substantial impact on local recurrences (18 in NAT versus 3 in WPRT), but had no impact on the risk of distant recurrence (18 NAT versus 11 in WPRT). Because of the lack of distant control, the use of WPRT did not impact overall survival (estimated 4 year survival 86% in NAT versus 92% in WPRT, p=0.557). The PORTEC trial randomized patients with intermediate-risk Stage I endometrial carcinoma to WPRT versus NAT. Of note, patients in this trial were not surgically staged. Of 714 patients with a median follow-up of 52 months,local recurrence rates were 4% in the WPRT group versus 14% in the control group (p<0.001). The use of WPRT did not impact 5-year overall survival (81% WPRT versus 85% NAT). Furthermore, some clinicians have advocated observation after surgical staging with radiation therapy reserved for those patients who recur locally. Several reports have reported salvage rates of 50-66% for patients with local recurrences. Given that approximately 20-25% patients in this population will recur locally, many clinicians prefer to use local radiation therapy as salvage therapy, thus sparing the majority of patients the potential long-term effects of pelvic radiation therapy. Given that radiation therapy does not affect distant metastasis and carries significant long-term morbidity, other therapies are necessary to improve disease-free survival in this setting. Adjuvant systemic chemotherapy is one potential option for these patients since it may sterilize both local and distant metastases. The use of adjuvant chemotherapy may be more desirable than radiation therapy because most side effects of chemotherapy are short-term and subside once therapy is completed or discontinued.
Multiple chemotherapeutic agents including cisplatin, doxorubicin HCL, paclitaxel, carboplatin, and oral etoposide have been studied for patients with advanced or recurrent endometrial cancer. A phase III study by the Gynecologic Oncology Group (GOG) compared doxorubicin with and without cisplatin (GOG 107) for patients with advanced or recurrent endometrial cancer. A higher response rate (42% vs. 25%) was noted for combination therapy and has been considered by many to be the standard chemotherapy regimen for treatment of patients with advanced endometrial cancer. Paclitaxel has also been studied as a single agent and in combination with platinum compounds in this setting. A phase II study that combined paclitaxel 175 mg/m2 as a 3-hour infusion with cisplatin 75 mg/m2 reported a 67% response rate. There were seven complete responses and nine partial responses with an 18-month median overall survival. An additional phase II study evaluated the efficacy of combining paclitaxel and carboplatin in both primary and recurrent non-papillary and papillary tumors following radiation therapy. the response rate was 78% in patients with primary advanced non-papillary tumors with a median disease-free survival of 23 months, with the median overall survival of 15 months. Currently, many clinicians are using a combination of paclitaxel, doxorubicin, and cisplatin (TAP), based on a phase III GOG study that demonstrated not only a significantly higher response rate (57% vs. 33%) over the combination of doxorubicin and cisplatin (AP), but also a survival advantage (median, 15.3 vs. 12.3 months; P=.037). Significantly more neurotoxicity was experienced by patients in the TAP arm. Currently, the GOG is evaluating the TAP combination versus the more tolerable regimen of paclitaxel and carboplatin in a phase III setting.
The combination of paclitaxel and carboplatin is considered the standard of care for both high-risk early stage ovarian cancer and advanced ovarian cancer. The safety of this combination is well established in a number of phase III trials and currently is used in the primary setting for patients with ovarian cancer and advanced endometrial cancer. Although this combination is considered active in endometrial carcinoma, there is a paucity of data regarding the use of adjuvant chemotherapy in the setting of intermediate-risk endometrial adenocarcinoma. Accordingly, this phase II study will evaluate the combination of paclitaxel and carboplatin as adjuvant therapy for patients with early stage adenocarcinoma of the endometrium at elevated-risk for recurrence.
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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Alabama
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Birmingham、Alabama、アメリカ、35233
- UAB Women's and Infant Center, 1700 6th Avenue South
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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
Inclusion Criteria:
- Patients must have a elevated risk, surgical stage II, stage IC, grade 2 or 3 adenocarcinoma of the endometrium.
- Patients must have undergone, a total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and a pelvic and para-aortic lymphadenectomy.
Patients must have adequate organ function defined as:
- Platelets >/= 100,000/µ
- Granulocytes (ANC)>/= 1,500/µl
- Creatinine</= 1.6 mg/dl
- SGOT (AST) </= 3x upper limits of normal
- Bilirubin within institutional normal limits
- Patients must have adequate performance status (ECOG performance status 0-2 or Karnofsky Performance Status >40)
- Patients must be age 19 or greater and have signed informed consent.
Exclusion Criteria:
- Patients with history of other malignancies within 5 years (except non- melanoma skin cancer or carcinoma-in-situ of the cervix) are ineligible.
- Patients with high-risk histologic subtypes of endometrial cancer such as papillary serous or clear cell histology are ineligible.
- Patients with histologic evidence of uterine sarcoma, including leiomyosarcoma, carcinosarcoma, endometrial stromal sarcoma, and adenosarcoma are ineligible.
- Patients who have received past pelvic radiotherapy are ineligible.
- Patients receiving any other investigational agents are ineligible.
- Patients with known hypersensitivity to paclitaxel and/or carboplatin are ineligible.
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:オープンラベル
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Paclitaxel will be administered at an appropriate dose (175 mg/m2) as a 3-hour continuous IV infusion every 21 days.
Carboplatin will be administered at an appropriate dose utilizing the Calvert formula for determining the area under the curve (AUC) based on the patient's glomerular filtration rate (GFR).
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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 |
---|---|---|
Disease-free Survival
時間枠:4 years - Median follow up time of 45.3 months
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Number of months of survival with no evidence of disease
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4 years - Median follow up time of 45.3 months
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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 |
---|---|---|
Toxicity
時間枠:4 years
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Toxicity secondary to paclitaxel and carboplatin based upon the NCI common toxicity criteria version
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4 years
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協力者と研究者
捜査官
- 主任研究者:John M. Straughn, MD、Assistant Professor, Dept of OB/Gyn, Division of GYN Oncology
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- F060328016 (UAB 0604)
- UAB 0604 (その他の識別子:UAB Department study number)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
子宮がんの臨床試験
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