- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01218048
ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
14. august 2018 oppdatert av: 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.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Detaljert 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.
Studietype
Intervensjonell
Registrering (Faktiske)
40
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Pennsylvania
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Pittsburgh, Pennsylvania, Forente stater, 15232
- UPCI - Hillman Cancer Center
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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 navn:
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
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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 |
Tiltaksbeskrivelse |
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.
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Up to 54 months
|
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Overall Survival (OS)
Tidsramme: Up to 2 years
|
Number of patients remaining alive.
|
Up to 2 years
|
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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.
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Up to 2 years
|
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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
|
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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)
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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)
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Rober L Ferris, MD, PhD, University of Pittsburgh Med Ctr (UPCI)
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. februar 2011
Primær fullføring (Faktiske)
4. november 2015
Studiet fullført (Faktiske)
14. februar 2017
Datoer for studieregistrering
Først innsendt
7. oktober 2010
Først innsendt som oppfylte QC-kriteriene
7. oktober 2010
Først lagt ut (Anslag)
8. oktober 2010
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
16. august 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
14. august 2018
Sist bekreftet
1. juli 2018
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter histologisk type
- Neoplasmer
- Neoplasmer etter nettsted
- Neoplasmer, kjertel og epitel
- Neoplasmer i hode og nakke
- Neoplasmer, plateepitelceller
- Karsinom
- Karsinom, plateepitel
- Plateepitelkarsinom i hode og nakke
- Antineoplastiske midler
- Antineoplastiske midler, immunologiske
- Karboplatin
- Cetuximab
Andre studie-ID-numre
- UPCI 08-013
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .