Circulating Tumor DNA-Informed Adjuvant Therapy for Intermediate-Risk Head and Neck Cancer
Phase II Trial of Drain Fluid Circulating Tumor DNA-Informed Adjuvant Therapy for Intermediate-Risk Head and Neck Cancer
This study is being done to determine whether an assay called LymphDetect™ Head and Neck is a useful tool to help guide treatment decisions for patients with head and neck cancer. The LymphDetect™ assay works to detect a certain kind of DNA that is released by tumors called circulating tumor DNA or ctDNA for short. In this study, the presence of ctDNA will be assessed in fluid collected from the surgical drain that will be placed during curative-intent surgical procedure performed as a part of patient standard care. Treatment after surgery is determined by a patient's disease risk category (low-risk, intermediate-risk, or high-risk). Having intermediate-risk with detection of ctDNA in the surgical drain fluid (SDF+) may mean that a patient is at greater risk of their cancer coming back. To reduce this risk, treatment will be more intensive than if ctDNA in the surgical drain fluid (SDF-) was not found.
調査の概要
状態
条件
詳細な説明
Patients who are Surgical Drain Fluid (SDF) positive have a more than eight-fold higher risk of Head and Neck Squamous Cell Carcinoma disease recurrence. Whether these pathologically intermediate-risk patients benefit from the addition of concurrent cisplatin to adjuvant radiotherapy is unknown. Various prognostic biomarkers have been proposed to identify patients at high risk of recurrence. Tissue-based biomarkers may be less prognostic after successful tumor extirpation. Several plasma-based ctDNA assays measuring treatment response in HPV- HNSCC are under investigation. However, data is limited on the role of such assays for the detection of molecular residual disease (MRD) after surgery, particularly for risk-informed adjuvant treatment decision making. Tumor-informed ctDNA from postoperative SDF, taken 24 hours after surgery, has been shown to be a promising biomarker for individualizing recurrence risk. The LymphDetect™ Head & Neck system, will be used to measure circulating tumor DNA (ctDNA) in surgical drain fluid, the most proximal biofluid to a recently resected tumor, to assess cancer recurrence risk at the source of potential spread - before it can travel to other parts of the body. There is a critical need to improve recurrence risk estimates for patients with HPV- HNSCC to inform the extent of adjuvant management, improve oncologic outcomes, and limit unnecessary treatment morbidity and mortality.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Jennifer Ruth, RN, BSN
- 電話番号：412-623-8963
- メール：ruthj2@upmc.edu
研究連絡先のバックアップ
- 名前：Mel J Mendez, RN, BSN
- 電話番号：878-261-6071
- メール：mendezmj@upmc.edu
研究場所
-
-
Pennsylvania
-
Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Hillman Cancer Center
-
コンタクト：
- Jennifer Ruth, RN, BSN
- 電話番号：412-623-8963
- メール：ruthj2@upmc.edu
-
コンタクト：
- Mel J Mendez, RN, BSN
- 電話番号：878-261-6071
- メール：mendezmj@upmc.edu
-
主任研究者：
- Kevin J Contrera, MD
-
-
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:
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Must have histologically or cytologically confirmed newly diagnosed mucosal HNSCC (i.e., oral cavity, oropharynx, hypopharynx, or larynx).
o Patients with intermediate-risk disease (stage cT2N0 with adverse pathologic features OR stage cT3-4Nany OR stage cTanyN1-3a) will be preferentially enrolled.
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Must have received no prior therapies for current malignancy, except for neoadjuvant pembrolizumab.
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Must be able to undergo curative-intent surgical resection with neck dissection and placement of a drain.
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Patient is considered a candidate for adjuvant chemotherapy (cisplatin) and radiation based on the clinical judgment of the treating investigator. This decision should be made based upon the patient's pre-operative assessment performed as part of the standard of care.
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Age ≥18 years.
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Performance status ECOG 0-2
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Sexually active, fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and for 30 days after the last dose of chemotherapy and/or radiation (whichever is later). In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
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Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
o Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years of age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
-
Must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- HPV-related oropharyngeal cancer
- Nasopharyngeal cancer
- Sinonasal cancer
- Prior or recurrent HNSCC
- Distant metastasis
- Other active malignancy, other than nonmetastatic skin, prostate, or thyroid malignancy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating 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：非ランダム化
- 介入モデル：並列代入
- 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：Low-Risk
|
A tumor-informed ctDNA assay that uses Surgical Drain Fluid (SDF) collected 24 hours after the end of surgery to direct therapeutic intervention. Performed within 28 days after baseline assessment to remove Head and Neck Cancer tumor(s). |
|
実験的：Intermediate Risk - Surgical Drain Fluid (negative)
IMRT or IMPT to 60 Gy in 30 fractions (2Gy/FX) ± Pembrolizumab - 200 mg q3w - Restart post-surgery (can begin prior to or at the same time as radiation therapy) and continue for up to 17 cycles (including neoadjuvant cycles). [IMRT / IMPT Schedule to be determined by radiation oncologist, should be completed within 42 days of start date] |
A tumor-informed ctDNA assay that uses Surgical Drain Fluid (SDF) collected 24 hours after the end of surgery to direct therapeutic intervention. Performed within 28 days after baseline assessment to remove Head and Neck Cancer tumor(s). Advanced type of radiation therapy that uses powerful energy beams to kill cancer cells. The energy can come from X-rays, protons or other sources, in which the beams of radiation are carefully customized. Humanized monoclonal antibody and a PD-1 inhibitor used in cancer immunotherapy that differs from chemotherapy as it does not directly kill cancer cells but stimulates the immune system, particularly T-cells, to recognize and attack cancer cells more effectively.
他の名前：
|
|
実験的：Intermediate Risk - Surgical Drain Fluid (positive)
IMRT or IMPT to 60 Gy in 30 fractions (2Gy/FX) with concurrent cisplatin 40 mg/m^2 weekly for 6 doses or 3-weekly 100mg/m2 dose for 3 doses ± Pembrolizumab - 200 mg q3w - Restart post-surgery (can begin prior to or at the same time as radiation therapy) and continue for up to 17 cycles (including neoadjuvant cycles). [Cisplatin: 40 mg/m^2 weekly (6 total doses) - Day 1, 8, 15, 22, 29, and 36 of radiation therapy or Cisplatin: 100 mg/m^2 q3w (3 total doses) - Day 1, 22, and 43 of radiation therapy (last dose of cisplatin may be after the last dose of radiation)] (If Cisplatin is not tolerated, Carboplatin AUC 2 weekly for 6 doses may be given.) |
A tumor-informed ctDNA assay that uses Surgical Drain Fluid (SDF) collected 24 hours after the end of surgery to direct therapeutic intervention. Performed within 28 days after baseline assessment to remove Head and Neck Cancer tumor(s). Advanced type of radiation therapy that uses powerful energy beams to kill cancer cells. The energy can come from X-rays, protons or other sources, in which the beams of radiation are carefully customized. Humanized monoclonal antibody and a PD-1 inhibitor used in cancer immunotherapy that differs from chemotherapy as it does not directly kill cancer cells but stimulates the immune system, particularly T-cells, to recognize and attack cancer cells more effectively.
他の名前：
An alkylating agent that contains platinum, which binds to DNA in cancer cells, causing cross-links that prevent DNA replication and repair, leading to cell death, particularly in rapidly dividing cancer cells.
他の名前：
|
|
実験的：High Risk
IMRT or IMPT to 60 Gy in 30 fractions (2Gy/FX) with concurrent cisplatin 40 mg/m^2 weekly for 6 doses or 3-weekly 100mg/m2 dose for 3 doses ± Pembrolizumab - 200 mg q3w - Restart post-surgery (can begin prior to or at the same time as radiation therapy) and continue for up to 17 cycles (including neoadjuvant cycles). [Cisplatin: 40 mg/m^2 weekly (6 total doses) - Day 1, 8, 15, 22, 29, and 36 of radiation therapy or Cisplatin: 100 mg/m^2 q3w (3 total doses) - Day 1, 22, and 43 of radiation therapy (last dose of cisplatin may be after the last dose of radiation)] (If Cisplatin is not tolerated, Carboplatin AUC 2 weekly for 6 doses may be given.) |
A tumor-informed ctDNA assay that uses Surgical Drain Fluid (SDF) collected 24 hours after the end of surgery to direct therapeutic intervention. Performed within 28 days after baseline assessment to remove Head and Neck Cancer tumor(s). Advanced type of radiation therapy that uses powerful energy beams to kill cancer cells. The energy can come from X-rays, protons or other sources, in which the beams of radiation are carefully customized. Humanized monoclonal antibody and a PD-1 inhibitor used in cancer immunotherapy that differs from chemotherapy as it does not directly kill cancer cells but stimulates the immune system, particularly T-cells, to recognize and attack cancer cells more effectively.
他の名前：
An alkylating agent that contains platinum, which binds to DNA in cancer cells, causing cross-links that prevent DNA replication and repair, leading to cell death, particularly in rapidly dividing cancer cells.
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 |
|---|---|---|
|
2-year Locoregional Control (LRC): SDF+ intermediate risk
時間枠：At 2 years
|
Proportion of patients without locoregional recurrence (growth or recurrence of the primary tumor or other nearby structures within the same anatomical region or nearby regional lymph nodes) at 2 years from the initiation of study treatment in patients who are SDF+ intermediate risk. |
At 2 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
2-year Locoregional Control (LRC): SDF- intermediate risk
時間枠：At 2 years
|
Proportion of patients without locoregional recurrence (growth or recurrence of the primary tumor or other nearby structures within the same anatomical region or nearby regional lymph nodes) at 2 years from the initiation of study treatment in patients who are SDF-intermediate risk. |
At 2 years
|
|
2-year Locoregional Control (LRC)
時間枠：At 2 years
|
Proportion of all patients without disease recurrence (growth or recurrence of the primary tumor or other nearby structures within the same anatomical region or nearby regional lymph nodes) at 2 years from the initiation of study treatment. |
At 2 years
|
|
2-year Event-free Survival (EFS): SDF+ intermediate risk
時間枠：At 2 years
|
Proportion of patients without disease recurrence (growth or recurrence of the primary tumor and nearby regional lymph nodes or other nearby structures within the same anatomical region), progression, or death from any cause in SDF+ intermediate risk patients at 2 years from the initiation of study treatment. |
At 2 years
|
|
2-year Event-free Survival (EFS): SDF- intermediate risk
時間枠：At 2 year
|
Proportion of patients without disease recurrence (growth or recurrence of the primary tumor and nearby regional lymph nodes or other nearby structures within the same anatomical region), progression, or death from any cause in SDF- intermediate risk patients at 2 years from the initiation of study treatment. |
At 2 year
|
|
2-year Event-free Survival (EFS)
時間枠：At 2 years
|
Proportion of all patients without disease recurrence (growth or recurrence of the primary tumor and nearby regional lymph nodes or other nearby structures within the same anatomical region), progression, or death from any cause at 2 years from the initiation of study treatment. |
At 2 years
|
|
2-year Overall Survival (OS): SDF+ intermediate risk
時間枠：At 2 years
|
Proportion of SDF+ intermediate risk patients alive at 2 years from the initiation of study treatment. |
At 2 years
|
|
2-year Overall Survival (OS): SDF- intermediate risk
時間枠：At 2 years
|
Proportion of SDF- intermediate risk patients alive at 2 years from the initiation of study treatment. |
At 2 years
|
|
2-year Overall Survival (OS)
時間枠：At 2 year
|
Proportion of all patients alive at 2 years from the initiation of study treatment. |
At 2 year
|
|
Incidence of Grade ≥ 3 Treatment-related Adverse Events (AE)
時間枠：up to 30 days post-treatment
|
Number of (distinct) HNSCC patients with grade ≥ 3 Treatment-related Adverse Events (AE)s per CTCAE v5.0. |
up to 30 days post-treatment
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Kevin J Contrera, MD、UPMC Cancer Center Hillman
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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 (実際)
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
- HCC 26-056
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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
米国で製造され、米国から輸出された製品。
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