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ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma

14 de agosto de 2018 actualizado por: 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.

Descripción general del estudio

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

40

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Pennsylvania
      • Pittsburgh, Pennsylvania, Estados Unidos, 15232
        • UPCI - Hillman Cancer Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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
Otros nombres:
  • ERBITUX®
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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
NK Cell Activation
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
Periodo de tiempo: 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)
Progression-free Survival (PFS)
Periodo de tiempo: Up to 54 months
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.
Up to 54 months
Overall Survival (OS)
Periodo de tiempo: Up to 2 years
Number of patients remaining alive.
Up to 2 years
Objective Response (Rate)
Periodo de tiempo: 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.
Up to 2 years
3-year Progression-free Survival (PFS)
Periodo de tiempo: 3 years
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.
3 years
Change in Tumor Size
Periodo de tiempo: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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)

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Colaboradores

Investigadores

  • Investigador principal: Rober L Ferris, MD, PhD, University of Pittsburgh Med Ctr (UPCI)

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de febrero de 2011

Finalización primaria (Actual)

4 de noviembre de 2015

Finalización del estudio (Actual)

14 de febrero de 2017

Fechas de registro del estudio

Enviado por primera vez

7 de octubre de 2010

Primero enviado que cumplió con los criterios de control de calidad

7 de octubre de 2010

Publicado por primera vez (Estimar)

8 de octubre de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

16 de agosto de 2018

Última actualización enviada que cumplió con los criterios de control de calidad

14 de agosto de 2018

Última verificación

1 de julio de 2018

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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