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

14. august 2018 opdateret af: 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.

Studieoversigt

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

40

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forenede Stater, 15232
        • UPCI - Hillman Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Andre navne:
  • 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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
NK Cell Activation
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: Up to 2 years
Number of patients remaining alive.
Up to 2 years
Objective Response (Rate)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

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

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. februar 2011

Primær færdiggørelse (Faktiske)

4. november 2015

Studieafslutning (Faktiske)

14. februar 2017

Datoer for studieregistrering

Først indsendt

7. oktober 2010

Først indsendt, der opfyldte QC-kriterier

7. oktober 2010

Først opslået (Skøn)

8. oktober 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. august 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. august 2018

Sidst verificeret

1. juli 2018

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Cetuximab

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