Phase I/II Study of Panitumumab, Capecitabine and Oxaliplatin w EBRT for Esophageal Cancer (POXX)

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Brian Czito, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00578071
First received: December 18, 2007
Last updated: January 20, 2013
Last verified: January 2013

December 18, 2007
January 20, 2013
December 2007
July 2011   (final data collection date for primary outcome measure)
  • Panitumumab Maximum Tolerated Dose in Milligrams (mg) [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
  • Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Within 30 days of the last day of radiation ] [ Designated as safety issue: Yes ]
  • Determine the maximal tolerated dose and recommended phase II dose for the combination of XRT/panitumumab/oxaliplatin/capecitabine for patients with resectable, locally advanced or metastatic esophageal/GE junction carcinoma [ Time Frame: 1 yr ] [ Designated as safety issue: Yes ]
  • Report the frequency and nature of grade 3-4 and grade 1-2 toxicities associated with panitumumab, oxaliplatin and capecitabine used in conjunction with radiation therapy. [ Time Frame: 3 yr ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00578071 on ClinicalTrials.gov Archive Site
  • Describe the 2 Year Overall Survival Rates for the Patients Studied on This Protocol. [ Time Frame: 2 yrs ] [ Designated as safety issue: No ]
    Number of patients alive two years after the date of diagnosis.
  • Pathological Complete Response Rates Associated With This Regimen. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Absence of residual viable tumor cells at the time of surgical resection of the esophagus performed 7-9 weeks following completion of chemoradiotherapy.
  • Describe the 1 year disease free and overall survival rates for the patients studied on this protocol. [ Time Frame: 3 yr ] [ Designated as safety issue: No ]
  • Estimate the radiographic and pathological response rates associated with this regimen. [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase I/II Study of Panitumumab, Capecitabine and Oxaliplatin w EBRT for Esophageal Cancer
A Phase I/II Study of Panitumumab, Capecitabine and Oxaliplatin Chemotherapy With External Beam Radiation Therapy for the Treatment of Resectable, Locally Advanced/Unresectable or Metastatic Esophageal Cancer

The primary purpose of this trial is to define the maximum tolerated and/or recommended phase II dose of the combination of panitumumab, oxaliplatin and capecitabine in patients undergoing radiation therapy for carcinoma of the thoracic esophagus or gastroesophageal junction. An additional primary objective is to describe the frequency and nature of grade III/IV and grade I/II toxicities associated with this regimen. Secondary objectives include describing 1-year disease-free survival and overall survival rates as well as to estimate clinical and pathologic complete response rates associated with this regimen.

This study has a phase I/II design. For this study the administration of panitumumab is considered investigational.

Pretreatment: Part of regular cancer care and disease staging includes Chest/Abdomen CT Scan, upper endoscopic ultrasound, PET scan, J-Tube Placement (if clinically indicated), bronchoscopy (per clinician judgment), ECG, and baseline laboratory studies.

During Treatment Weeks 1-5.5 of Radiation Therapy(RT)/Chemotherapy:

  • RT (180 cGy/fx, Mon-Fri) days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38.
  • Panitumumab (per dose level) days 1, 15, 29.
  • Oxaliplatin (per dose level) days 1, 8, 15, 22, 29, 36.
  • Capecitabine (per dose level M-F) 1-5, 8-12, 15-19, 22-26, 29-33, 36-38.
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer of the Esophagus
  • Drug: Panitumumab
    Dose per cohort level (3.6, 4.8 or 6.0 mg/kg ), given intravenously (IV) days 1, 15 and 29 of radiation.
  • Drug: Capecitabine
    Dose per cohort level (500, 625 or 825 mg/m2) taken by mouth twice each day of radiation
    Other Name: Xeloda
  • Drug: Oxaliplatin
    Dose per cohort level (30, 40, or 50 mg/m2). Given IV one day each week during radiation
  • Radiation: Radiation Therapy (RT)
    Daily for 6 weeks
Experimental: Treatment
panitumumab, oxaliplatin, capecitabine and EBRT
Interventions:
  • Drug: Panitumumab
  • Drug: Capecitabine
  • Drug: Oxaliplatin
  • Radiation: Radiation Therapy (RT)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
June 2012
July 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18 years of age or older.
  • Histologically or cytologically documented squamous cell carcinoma or Siewert's classification adenocarcinoma of the esophagus or proximal stomach T1-4, N0-2, M0-1, for which bimodality treatment with chemotherapy and radiation therapy is indicated.
  • Measurable Disease
  • ECOG Performance Status 0-1
  • Laboratory values must be as follows:
  • Absolute neutrophil count > or = 2,000/mm3,
  • Platelets > or = 100,000/mm3,
  • Hemoglobin > 9.0,
  • Total bilirubin <1.5 x institutional upper normal limit,
  • Serum creatinine <1.5 x institutional upper normal limit,
  • AST or ALT < 3x institutional upper normal limit,
  • Magnesium equal or higher than institutional lower limit,
  • Creatinine clearance Estimated > 40 ml/min,
  • Calcium > lower limit of normal.
  • Not pregnant or lactating. Negative pregnancy test within 72 hours prior to registration (female patients of childbearing potential). Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Life expectancy must be >3 months.
  • No serious or poorly controlled medical or psychological conditions that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
  • Able to swallow capecitabine (whole or crushed tablet or liquid dispersed) or patients may have a G or J tube.
  • No conditions that would significantly compromise intestinal absorption of the study drugs.

Exclusion Criteria:

  • Tumors extending above the level of the thoracic inlet or beyond 5 cm below the gastroesophageal junction.
  • Patients with radiographic or bronchoscopic evidence of esophageal perforation.
  • Patients with known evidence of brain metastases, lymphangitic lung metastases, or carcinomatous meningitis.
  • Dementia or significantly altered mental status
  • Major surgery within 4 weeks of the start of study treatment
  • Prior chemotherapy, radiation therapy, hormonal or biologic therapy within the past 6 months.
  • Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine, corticosteroids)
  • Currently requiring medications that may interact with the metabolism or disposition of capecitabine/5-FU: dipyridamole, folinic acid, allopurinol, trimethoprim, misonidazole, metoclopramide, flucytosine or cimetidine.
  • Hypersensitivity to platinum containing compounds or capecitabine or any of the excipients of this product. Prior unanticipated severe reaction to fluoropyrimidine/platinum therapy, or known sensitivity to 5-fluorouracil/platinum containing compounds.
  • Serious, uncontrolled, concurrent infection(s).
  • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  • Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
  • Peripheral neuropathy > grade 1
  • Any of the following within 24 weeks before randomization: clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia).
  • Uncontrolled gastrointestinal ulcer within 28 days of randomization
  • History of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
  • Preexisting known bleeding diathesis or coagulopathy
  • Plans to continue on or use of ketoconazole, phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin or St. John's Wort, 14 days prior to randomization.
  • History of hypersensitivity to tetracyclines
  • Subject known to be human immunodeficiency virus positive
  • Subjects known to have chronic or active hepatitis B or C infection
Both
18 Years to 82 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00578071
Pro00002207, SPS 151596
No
Brian Czito, Duke University Medical Center
Brian Czito
Amgen
Principal Investigator: Brian Czito, MD Duke University
Duke University
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP