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
  Purpose

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.


Condition Intervention Phase
Cancer of the Esophagus
Drug: Panitumumab
Drug: Capecitabine
Drug: Oxaliplatin
Radiation: Radiation Therapy (RT)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 29
Study Start Date: December 2007
Study Completion Date: June 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
panitumumab, oxaliplatin, capecitabine and EBRT
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

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 82 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578071

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Brian Czito
Amgen
Investigators
Principal Investigator: Brian Czito, MD Duke University
  More Information

No publications provided

Responsible Party: Brian Czito, Associate Professor, Radiation Oncology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00578071     History of Changes
Other Study ID Numbers: Pro00002207, SPS 151596
Study First Received: December 18, 2007
Results First Received: April 10, 2012
Last Updated: January 20, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Oxaliplatin
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014