- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01218048
ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
14 août 2018 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
40
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, États-Unis, 15232
- UPCI - Hillman Cancer Center
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-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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 d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
Autres noms:
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
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
NK Cell Activation
Délai: 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
Délai: 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
Délai: 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)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
Délai: 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)
Délai: 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)
Délai: Up to 2 years
|
Number of patients remaining alive.
|
Up to 2 years
|
|
Objective Response (Rate)
Délai: 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)
Délai: 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
Délai: 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)
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Rober L Ferris, MD, PhD, University of Pittsburgh Med Ctr (UPCI)
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 février 2011
Achèvement primaire (Réel)
4 novembre 2015
Achèvement de l'étude (Réel)
14 février 2017
Dates d'inscription aux études
Première soumission
7 octobre 2010
Première soumission répondant aux critères de contrôle qualité
7 octobre 2010
Première publication (Estimation)
8 octobre 2010
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
16 août 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
14 août 2018
Dernière vérification
1 juillet 2018
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Tumeurs par site
- Tumeurs, glandulaires et épithéliales
- Tumeurs de la tête et du cou
- Tumeurs à cellules squameuses
- Carcinome
- Carcinome épidermoïde
- Carcinome épidermoïde de la tête et du cou
- Agents antinéoplasiques
- Agents antinéoplasiques immunologiques
- Carboplatine
- Cétuximab
Autres numéros d'identification d'étude
- UPCI 08-013
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .