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.
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Jennifer Ruth, RN, BSN
- Telefonní číslo: 412-623-8963
- E-mail: ruthj2@upmc.edu
Studijní záloha kontaktů
- Jméno: Mel J Mendez, RN, BSN
- Telefonní číslo: 878-261-6071
- E-mail: mendezmj@upmc.edu
Studijní místa
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Pennsylvania
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Pittsburgh, Pennsylvania, Spojené státy, 15232
- UPMC Hillman Cancer Center
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Kontakt:
- Jennifer Ruth, RN, BSN
- Telefonní číslo: 412-623-8963
- E-mail: ruthj2@upmc.edu
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Kontakt:
- Mel J Mendez, RN, BSN
- Telefonní číslo: 878-261-6071
- E-mail: mendezmj@upmc.edu
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Vrchní vyšetřovatel:
- Kevin J Contrera, MD
-
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
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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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Low-Risk
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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). |
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Experimentální: 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.
Ostatní jména:
|
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Experimentální: 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.
Ostatní jména:
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.
Ostatní jména:
|
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Experimentální: 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.
Ostatní jména:
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.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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2-year Locoregional Control (LRC): SDF+ intermediate risk
Časové okno: At 2 years
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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
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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2-year Locoregional Control (LRC): SDF- intermediate risk
Časové okno: 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
|
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2-year Locoregional Control (LRC)
Časové okno: At 2 years
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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
|
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2-year Event-free Survival (EFS): SDF+ intermediate risk
Časové okno: At 2 years
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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
|
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2-year Event-free Survival (EFS): SDF- intermediate risk
Časové okno: At 2 year
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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
|
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2-year Event-free Survival (EFS)
Časové okno: At 2 years
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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
|
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2-year Overall Survival (OS): SDF+ intermediate risk
Časové okno: At 2 years
|
Proportion of SDF+ intermediate risk patients alive at 2 years from the initiation of study treatment. |
At 2 years
|
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2-year Overall Survival (OS): SDF- intermediate risk
Časové okno: At 2 years
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Proportion of SDF- intermediate risk patients alive at 2 years from the initiation of study treatment. |
At 2 years
|
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2-year Overall Survival (OS)
Časové okno: At 2 year
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Proportion of all patients alive at 2 years from the initiation of study treatment. |
At 2 year
|
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Incidence of Grade ≥ 3 Treatment-related Adverse Events (AE)
Časové okno: up to 30 days post-treatment
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Number of (distinct) HNSCC patients with grade ≥ 3 Treatment-related Adverse Events (AE)s per CTCAE v5.0. |
up to 30 days post-treatment
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Kevin J Contrera, MD, UPMC Cancer Center Hillman
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary podle místa
- Novotvary
- Novotvary hlavy a krku
- Organické chemikálie
- Terapeutika
- Anorganické chemikálie
- Sloučeniny chloru
- Sloučeniny dusíku
- Koordinační komplexy
- Platinové sloučeniny
- Radioterapie
- Radioterapie, konformní
- Radioterapie, asistovaná počítačem
- Karboplatina
- Cisplatina
- Pembrolizumab
- Radioterapie, modulovaná intenzita
Další identifikační čísla studie
- HCC 26-056
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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