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Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

29 juin 2018 mis à jour par: Wake Forest University Health Sciences

A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with oxaliplatin, fluorouracil, and radiation before surgery and alone after surgery in treating patients with locally advanced cancer of the esophagus and gastroesophageal junction. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with erlotinib hydrochloride and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib hydrochloride after surgery may kill any tumor cells that remain after surgery

Aperçu de l'étude

Description détaillée

OBJECTIVES:

I. The primary aim of this phase I study is to evaluate the safety of multi-drug chemotherapy (with the addition of an anti-epidermal growth factor receptor [EGFR] agent erlotinib [erlotinib hydrochloride]) and concomitant radiotherapy followed by resection and consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment tumor cyclin D1 expression and EGFR expression/amplification.

III. Correlate pathologic complete response with changes in fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and post-chemoradiation.

OUTLINE: This is a dose escalation study of erlotinib hydrochloride

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (PO) QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.

SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor.

CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Type d'étude

Interventionnel

Inscription (Réel)

9

Phase

  • La phase 1

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

    • North Carolina
      • Winston-Salem, North Carolina, États-Unis, 27157
        • Wake Forest University Health Sciences

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:

  • Newly diagnosed patients with locally advanced esophageal cancer with either squamous or adenocarcinoma histology; patients should have evidence of extension of disease into or through the wall of the esophagus (T2-4) and/or regional nodal metastasis (N1)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Non-pregnant; patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method); nursing mothers are also ineligible
  • Prior treatment: Greater than one week shall have elapsed since any major surgery; no prior chemotherapy or radiotherapy is allowed
  • Adequate whole blood cell (WBC) and platelets (Plt) as determined by medical oncology
  • Serum creatinine =< 1.5 mg/dl
  • Creatinine clearance >= 60 ml/min
  • Hemoglobin (Hgb) >= 9.0 gm/dl
  • Absolute neutrophil count >= 1,500/uL
  • Serum total bilirubin =< 1.5 mg/dL
  • Alkaline phosphatase =< 3X the upper limit of normal (ULN) for the reference lab
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 2X ULN for the reference laboratory
  • Patients must be told of the investigational nature of the study and must sign a written informed consent
  • No serious medical or psychiatric illnesses which would prevent informed consent or otherwise limit survival to less than two years; no history of refractory congestive heart failure or cardiomyopathy
  • Patients should be evaluated by medical oncology, radiation oncology, and surgery, and felt to by all to be suitable for trimodality therapy

Exclusion Criteria:

Patients with an active infection or with a fever >= 38.5 degrees Celsius (C) within 3 days of the first scheduled day of protocol treatment

  • History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate surface antigen (PSA) of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry
  • Patients with known hypersensitivity to any of the components of oxaliplatin
  • Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
  • Peripheral neuropathy >= Grade 2
  • History of allogeneic transplant
  • Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
  • Pregnancy

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: Treatment (chemotherapy, enzyme inhibitor therapy)

CHEMORADIOTHERAPY: Patients undergo radiation therapy QD, 5 days a week and receive fluorouracil IV continuously and erlotinib hydrochloride PO QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.

SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor.

CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

Étant donné IV
Autres noms:
  • 1-OHP
  • Dacotine
  • Dacplat
  • Eloxatine
  • L-OHP
Étant donné IV
Autres noms:
  • 5-FU
  • 5-fluorouracile
  • 5-Fluracil
Subir une radiothérapie
Autres noms:
  • irradiation
  • radiothérapie
  • thérapie, radiothérapie
Bon de commande donné
Autres noms:
  • OSI-774
  • erlotinib
  • CP-358,774
Étude corrélative
Étude corrélative
Autres noms:
  • immunohistochimie
Undergo surgical resection
Autres noms:
  • chirurgie conventionnelle
Correlative study
Autres noms:
  • ANIMAUX
  • FDG-PET
  • TEP-scan
  • tomographie, émission calculée
Correlative study
Autres noms:
  • tomographie, calculée
Correlative study
Undergo F18 PET and CT scan
Autres noms:
  • 18FDG
  • FDG

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride
Délai: Approximately 6 months
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any >= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.
Approximately 6 months

Mesures de résultats secondaires

Mesure des résultats
Délai
Time to progression
Délai: Approximately 4 years
Approximately 4 years
Survival
Délai: Approximately 4 years
Approximately 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
Délai: Over 4 years
Over 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
Délai: Approximately 1 year
Approximately 1 year
Test the predictive value of FDG-PET-CT imaging in identifying patients who will have a complete response
Délai: Approximately 1 year
Approximately 1 year

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

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 (Réel)

1 avril 2007

Achèvement primaire (Réel)

1 mars 2009

Achèvement de l'étude (Réel)

1 mars 2009

Dates d'inscription aux études

Première soumission

14 février 2012

Première soumission répondant aux critères de contrôle qualité

21 mars 2012

Première publication (Estimation)

22 mars 2012

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 juillet 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 juin 2018

Dernière vérification

1 juin 2018

Plus d'information

Termes liés à cette étude

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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 .

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