Celecoxib and Docetaxel or Pemetrexed in Treating Patients With Advanced Recurrent Non-Small Cell Lung Cancer
A Phase II Trial of Celecoxib Plus Chemotherapy [Docetaxel or Pemetrexed] in Patients With Previously Treated, "COX Dependent" Recurrent Non-Small Cell Lung Cancer
RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes need for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving celecoxib together with docetaxel or pemetrexed may kill more tumor cells.
PURPOSE: This phase II trial is studying how well celecoxib given together with docetaxel or pemetrexed works in treating patients with advanced or recurrent non-small cell lung cancer.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- To determine the efficacy of celecoxib when administered with standard chemotherapy comprising docetaxel or pemetrexed disodium in patients with advanced, recurrent non-small cell lung cancer (NSCLC) exhibiting cyclooxygenase (COX) dependence.
Secondary
- To determine the overall response rate and time to progression in patients with COX-dependent recurrent NSCLC treated with celecoxib and docetaxel or pemetrexed disodium.
- To determine the effect of celecoxib on the urinary metabolites of PGE_2 , PGI_2, and thromboxane in patients with COX-dependent recurrent NSCLC.
- To correlate changes in urinary PGE-M and survival with intratumoral expression of COX-2, mPGES, and 15-PGDH as assessed by IHC.
OUTLINE: Patients with no prior taxane exposure receive docetaxel IV over 1 hour on day 1; patients with prior taxane exposure or for whom docetaxel treatment is contraindicated receive pemetrexed disodium IV over 10 minutes on day 1. Treatment with docetaxel or pemetrexed disodium repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral celecoxib twice daily beginning 5-7 days prior to the first docetaxel or pemetrexed disodium infusion and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and urine sample collection at baseline and periodically during study for biomarker correlative studies. Urine samples are assessed for PGE-M levels. Blood samples are analyzed for serum celecoxib levels, VEGF, endostatin, and cytokine assays.
After completing the last dose of celecoxib, patients are followed at 4-6 weeks and then every 3 months thereafter for up to 2 years from study entry.
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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Tennessee
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Nashville、Tennessee、アメリカ、37232-6838
- Vanderbilt-Ingram Cancer Center
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Nashville、Tennessee、アメリカ、37064
- Vanderbilt-Ingram Cancer Center - Cool Springs
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Nashville、Tennessee、アメリカ、37064
- Vanderbilt-Ingram Cancer Center at Franklin
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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
Eligibility Criteria:
- Cytologically or histologically confirmed "COX dependent" non-small cell lung cancer.
- COX dependency is defined by change in urinary PGE-M levels following a "run-in" phase of celecoxib.
- Previous treatment with ≤2 different chemotherapy regimens one of which must have been platinum-based (cisplatin or carboplatin) chemotherapy.
- Age ≥18 years
- ECOG PS 0, 1 or 2.
- Measurable or evaluable disease.
- At least 3 weeks post major surgery, chemotherapy or radiotherapy & recovered from all toxicities.
- Expected survival of at least 2 months.
- CNS metastases permitted provided the patient has adequately recovered from radiotherapy includes stereotactic therapy) or surgery.
- Adequate renal function: serum creatinine ≤1.8 mg/dl &/or CrCl >50 cc/min
Eligibility According to Liver Function:
AST:
</= 1.5 ULN-Docetaxel; </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 5.0 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)
Alk Phosphatase:
</= 2.5 ULN-Docetaxel; </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 5.0 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)
Total Bilirubin:
</= 1.5 ULN-Docetaxel; </= 1.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)
- Adequate hematologic function: ANC≥1500/mm3 & platelets ≥100,000/mm3
- Female patients cannot be pregnant and must use contraception if of childbearing age
- Lactating women are excluded.
- Peripheral neuropathy must be CTC grade ≤2
- Patients must not currently be on non-steroidal anti-inflammatory agents or other COX-2 inhibitors (Must be off for at least ≤7 days)
- Written informed consent.
Exclusion Criteria:
- More than two prior chemotherapy regimens for recurrent or relapsed NSCLC.
- COX Independent as defined by change in urinary PGE-M levels following a "run-in" phase of celecoxib.
- Previous treatment with both docetaxel and pemetrexed
- History of greater than grade 2 allergic reaction to celecoxib or any other non-steroid anti-inflammatory agent including aspirin, ibuprofen, or indomethacin.
- History of allergy to compounds containing boron or mannitol.
- History of allergy to sulfonamides.
- Concomitant use of Warfarin, but low dose Coumadin allowed for port prophylaxis
- Recent (past 4 weeks) coronary artery bypass graft (CABG) surgery.
- Inadequate organ function:
- Serum creatinine ≥1.8 mg/dl or a calculated CrCl <45 cc/min.
- AST >1.5 upper limits of normal (ULN); alkaline phosphatase >2.5 ULN; & bilirubin >1.5 ULN
- ANC<1500/mm3 & platelets <100,000/mm3
- Active pregnancy or inability or unwillingness to employ appropriate contraception.
- Small cell carcinoma histology.
- Prior malignancy within 5 years of diagnosis of NSCLC. Exceptions include basal cell or non-metastatic squamous cell carcinomas of the skin, cervical carcinoma in situ or FIGO stage I cervical carcinoma, or other cancer history considered not clinically significant by the principal investigator.
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 |
---|---|
実験的:Treatment Arm
Either docetaxel or pemetrexed given with celecoxib
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採血
600 mg will be taken by mouth twice a day for 6 weeks then 400 mg twice a day for up to a year after chemotherapy is discontinued in the absence of progression.
75mg/m2 given through a vein over 90 minutes on day 1 of a 3-week cycle
500 mg/m2 through a vein over 90 minutes on day 1 of a 3 week cycle.
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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 |
---|---|---|
Median Survival
時間枠:2 years from date of registration
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Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)
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2 years from date of registration
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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 |
---|---|---|
Overall Response Rate
時間枠:On-treatment date to date of disease progression (assessed at 6 weeks up to 2 years)
|
Overall response rate is measured by complete response + partial response.
Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD.
Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD.
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On-treatment date to date of disease progression (assessed at 6 weeks up to 2 years)
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Time to Progression
時間枠:2 years from date of registration
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Estimated probable duration from on-study date to date of disease progression, using the Kaplan-Meier method with censoring (see analysis population description for additional details).
Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.
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2 years from date of registration
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その他の成果指標
結果測定 |
時間枠 |
---|---|
Effect of Celecoxib on Urinary Metabolites of PGE2, PG12 and Thromboxane
時間枠:At 1 year
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At 1 year
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Changes in Urinary PGE-M and Survival as Assessed by Immunohistochemistry
時間枠:At 1 year
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At 1 year
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協力者と研究者
捜査官
- スタディチェア:Leora Horn, MD、Vanderbilt-Ingram Cancer Center
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 (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
追加の関連 MeSH 用語
その他の研究ID番号
- VICC THO 0730
- P30CA068485 (米国 NIH グラント/契約)
- VU-VICC-THO-0730
- VU-VICC-IRB-070723
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。
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