ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
2018年8月14日 更新者:Robert Ferris
Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma
There are currently no useful tests to identify patients who will respond to cetuximab therapy, notably because EGFR levels do not correlate with the clinical responses observed.
Thus, the investigators are investigating the role of cellular immunity and immune escape mechanisms to explain the differential clinical response to cetuximab.
調査の概要
状態
完了
条件
詳細な説明
This prospective phase II clinical trial of preoperative, single-agent cetuximab treated patients is being conducted in order to obtain specimens before and after 4 weeks of cetuximab for immune biomarker studies.
Stage III/IV HNC patients will be treated with definitive surgical resection and observed for disease recurrence.
Cetuximab will be administered for a 3-4 week preoperative period to study biomarker modulation in correlation clinical response by CT scan and tumor apoptosis/proliferation after tumor excision, immediately after neoadjuvant cetuximab but before surgery.
We will biopsy the skin/acneiform rash in all patients to correlate rash with biomarker modulation and clinical response.
Cetuximab may also be given in the adjuvant setting.
A primary scientific hypothesis will be tested: does short term pre-operative exposure to cetuximab modulate blood immune biomarkers and is immune modulation associated with anti-tumor effect?
Forty (n=40) patients with complete specimens (tumor, peripheral blood mononuclear cells (PBMC) and serum) are necessary to enable adequate statistical power to be reached using paired specimens.
A secondary set of hypotheses will evaluate the association between pre-operative biomarker levels and modulation with disease recurrence.
The proposed trial will accrue stage II, III or IV surgical candidates without distant metastasis.
研究の種類
介入
入学 (実際)
40
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- UPCI - Hillman Cancer Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).
- Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.
- Macroscopic complete resection of the primary tumor must be planned.
- Age greater than or equal to 18 years.
- ECOG performance status 0-1.
Adequate hematologic, renal and hepatic function, as defined by:
- Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.
- Creatinine clearance > 40
- Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.
- Have signed written informed consent.
Exclusion Criteria:
- Subjects who fail to meet the above criteria.
- Prior severe infusion reaction to a monoclonal antibody.
- Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
- All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.
- Subjects with an ECOG performance status of 2 or worse.
- Evidence of distant metastasis.
- Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.
- Prior history of HNC.
- Prior therapy targeting the EGFR pathway.
- Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
- Acute hepatitis, known HIV, or active uncontrolled infection.
- History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
- Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.
- Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.
- Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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:Neo-Adjuvant Cetuximab
Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. |
Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT
他の名前:
Surgery for tumor
Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery
Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
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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 |
|---|---|---|
|
NK Cell Activation
時間枠:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
|
Serum Cytokines Levels
時間枠:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
|
T Cell Activation
時間枠:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
T cell activation measured at pre-/post-cetuximab exposure
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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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 |
|---|---|---|
|
Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
時間枠:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
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Progression-free Survival (PFS)
時間枠:Up to 54 months
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The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
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Up to 54 months
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Overall Survival (OS)
時間枠:Up to 2 years
|
Number of patients remaining alive.
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Up to 2 years
|
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Objective Response (Rate)
時間枠:Up to 2 years
|
The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response.
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Up to 2 years
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3-year Progression-free Survival (PFS)
時間枠:3 years
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Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
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3 years
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Change in Tumor Size
時間枠:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab.
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者:Rober L Ferris, MD, PhD、University of Pittsburgh Med Ctr (UPCI)
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2011年2月1日
一次修了 (実際)
2015年11月4日
研究の完了 (実際)
2017年2月14日
試験登録日
最初に提出
2010年10月7日
QC基準を満たした最初の提出物
2010年10月7日
最初の投稿 (見積もり)
2010年10月8日
学習記録の更新
投稿された最後の更新 (実際)
2018年8月16日
QC基準を満たした最後の更新が送信されました
2018年8月14日
最終確認日
2018年7月1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
- UPCI 08-013
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