Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)
A Randomized Phase 2 Trial of Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma
The goal of this clinical research study is to compare pazopanib to temsirolimus in the treatment of advanced clear-cell renal cell carcinoma. The safety of each drug will also be studied.
Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.
Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.
This is an investigational study. Pazopanib and temsirolimus are both FDA approved and commercially available for the treatment of kidney cancer. It is investigational to compare the 2 drugs.
Up to 90 patients will be enrolled in this study. All will be enrolled at MD Anderson.
調査の概要
詳細な説明
Study Groups and Study Drug Administration:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group.
- If you are assigned to Group 1, you will take pazopanib by mouth 1 time every day at about the same time each day on an empty stomach (at least 1 hour before or 2 hours after a meal).
- If you are assigned to Group 2, you will receive temsirolimus by vein 1 time every week over 30-60 minutes. About 30 minutes before you receive each dose of temsirolimus, you will receive Benadryl (diphenhydramine) by vein over 1-2 minutes to help lower the risk of side effects.
If you are assigned to Group 1, do not crush tablets and do not repeat missed doses if it is less than 12 hours until your next scheduled dose. You will be given a pill diary to record when you take each dose. You will return the diary to the study doctor at each study visit.
If you have any side effects, you should tell the study doctor right away. If the study doctor thinks it is in your best interest, your dose may be lowered.
If the disease gets worse while you are on study, you will have the option to change to the study group you were not originally assigned to and take the other study drug. The study drug dosing and study visit schedule will be the same, and the study doctor will discuss any important details with you at the time you change study groups.
Study Visits:
Every 4 weeks on this study is called a study cycle.
Every week during Cycle 1 (Group 1 only), your blood pressure will be checked (either at home, at the clinic, or by your local doctor). If you are checking your own blood pressure at home, you will need to write down your blood pressure in a blood pressure diary each time you check it and bring the diary with you to each clinic visit.
Every 2 weeks for the first 2 cycles (Group 1 only) , blood (about 3 tablespoons) will be drawn for routine tests.
Every week (Group 2 only), blood (about 1 tablespoon) will be drawn for routine tests.
Every cycle (Group 2 only) OR Every other cycle (Group 1 only):
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs or treatments you may be receiving.
- You will be asked about any side effects you may have had.
- Blood (about 3 tablespoons) will be collected for routine tests.
On Day 1 of Cycle 2, Day 1 of Cycle 4, and every 4 cycles after that (Group 1 only), you will have an ECG to check your heart function.
If you are in Group 2 only, on Day 1 of Cycles 2, 3, and every other cycle after that (Cycles 5, 7, 9, and so on), blood (about 3 tablespoons) will be drawn for routine tests. You will be asked to fast (eat nothing and drink only water) for at least 8 hours before those blood draws.
Every 2 cycles:
- You will have the same imaging scans that you had at screening. After 1 year on treatment, these imaging scans may only be done every 3 cycles (Cycles 5, 8, 11, and so on).
- You will fill out the quality-of-life questionnaires.
- Blood (about 2 teaspoons) will be drawn for tests to check your thyroid function (Group 1 only).
- Urine will be collected for routine tests.
Every 4 cycles, you will have an ECG (Group 2 only).
Every 6 cycles, you will have an ECHO or MUGA scan to check your heart function.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take a study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
End-of-Treatment Follow- up:
About 30 days after you stop treatment, during a clinic visit or by phone, you will be asked about any drugs or treatments you may be receiving and any side effects you may have had.
Long-Term Follow-up:
After you stop taking the study drug, the study staff will check up on you to ask how you are doing about every 3 months from then on. The study staff will collect the information they need either from your medical records or by calling you. If you are contacted by phone, the call should only last about 5 minutes.
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
-
-
Texas
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Houston、Texas、アメリカ、77030
- University of Texas MD Anderson Cancer Center
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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:
- Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component.
- Measurable disease by RECIST criteria.
- Age >/= 18 years
- ECOG performance status 0-2 or Karnofsky Performance Status >/= 60%
- Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH > 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level > upper limit of normal), time from initial RCC diagnosis to registration on this trial < 1 year, and > 1 metastatic organ sites.
- Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count >/=1,500/µL b) Platelets >/=100,000/µL c) Hgb >/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine </= 1.5 x ULN or calculated CrCl >/= 40 cc/min and random urine protein:creatinine ratio (UPC) < 1 or 24-hr urine protein < 1g e) Liver: total bilirubin </= 1.5 mg/dl; AST (SGOT) and ALT (SGPT) </= 2.5 x ULN for subjects without evidence of liver metastases, </= 5 x ULN for subjects with documented liver metastases f) INR </= 1.2 x ULN; PTT </= 1.5 x ULN. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of randomization.
- Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed > 14 days before starting study drug.
Exclusion Criteria:
- Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years
- Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed.
- Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed.
- Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration.
- History of stroke within 6 months of registration
- Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist.
- Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted.
- History of uncontrolled hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- Significant vascular disease including aortic aneurysm, aortic dissection.
- Symptomatic peripheral vascular disease
- Pregnancy
- HIV-positive patients receiving combination anti-retroviral therapy
- Coagulopathy or bleeding diathesis
- Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
- Major surgery within 28 days prior to registration
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to starting drug
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration
- Serious non-healing wound
- Baseline QTcB >/= 470 msec.
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：ランダム化
- 介入モデル：クロスオーバー割り当て
- 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 |
|---|---|
|
実験的：Pazopanib
Pazopanib 800 mg by mouth daily.
Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
|
800 mg by mouth daily in 4 week study cycle.
他の名前：
Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
他の名前：
|
|
実験的：Temsirolimus
Temsirolimus 25 mg by vein infused over 30-60 minutes weekly.
Benadryl 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.
Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
|
Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
他の名前：
25 mg by vein infused over 30-60 minutes every week in 4 week study cycle.
他の名前：
25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.
他の名前：
|
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 |
|---|---|---|
|
Progression Free Survival (PFS)
時間枠：Measured form start of treatment up to 3 years
|
PFS is measured from the initiation of treatment to the time of first disease progression or death due to any reason during the first drug administration in each arm.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% or more increase in the sum of the longest diameters of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions.
The PFS median of first drug pazopanib (treatment group) was compared to the PFS median of first drug temsirolimus (control group) in an adjusted Hazard ratio.
The hazard ratio compares events from a treatment group to a control group.
If the hazard ratio is greater than 1the treatment group performed better.
If the hazard ratio is less than 1 the control group performed better.
If the hazard ratio is equal to 1, then the groups performed equally.
|
Measured form start of treatment up to 3 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival (OS)
時間枠：From the start of treatment up to 6 years or death, whichever came first
|
Overall survival is calculated from day of therapy initiation of the first administrated drug to the date of death.
Kaplan-Meier estimator used to estimate the OS for each group of participants.
The Overall Survival median of first drug pazopanib (treatment group) was compared to the Overall Survival median of first drug temsirolimus (control group) in an adjusted Hazard ratio.
The hazard ratio compares events from a treatment group to a control group.
If the hazard ratio is greater than 1the treatment group performed better.
If the hazard ratio is less than 1 the control group performed better.
If the hazard ratio is equal to 1, then the groups performed equally.
|
From the start of treatment up to 6 years or death, whichever came first
|
協力者と研究者
協力者
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 (実際)
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 (実際)
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2011-0358
- NCI-2011-01277 (レジストリ識別子：NCI CTRP)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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