Chemoradiation and Panitumumab for Esophageal Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01077999
First received: February 25, 2010
Last updated: September 7, 2010
Last verified: September 2010
  Purpose

A consistent finding in many studies in patients with operable esophageal and gastro-esophageal junction (GEJ) cancer is that response to preoperative therapy, particularly the absence of residual disease in the surgical specimen, is an indicator of better disease-free and overall survival. Therefore in the investigators trial the investigators will evaluate the pathologic response of panitumumab in combination with neoadjuvant chemoradiation as first line treatment of operable adenocarcinomas, undifferentiated or squamous cell carcinomas of the esophagus.


Condition Intervention Phase
Squamous Cell Carcinoma
Adenocarcinoma
Esophageal Cancer
Gastro-esophageal Junction Cancer
Drug: carboplatin
Drug: Paclitaxel
Drug: Panitumumab
Radiation: 3-D conformal radiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemoradiation Combined With Panitumumab Followed by Surgery for Patients With Operable Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Percentage of pathologic complete responses [ Time Frame: 6 weeks after the completion of the chemoradiation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • R0 resection rate [ Time Frame: the pathologist will determine the resection rate ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: Every 3 months during the first 2 years after surgery, and every 6 months thereafter. ] [ Designated as safety issue: No ]
  • Toxicity profile [ Time Frame: Weekly during chemoradiation. After surgery: every 3 months during the first 2 years after surgery, and every 6 months thereafter. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 76
Study Start Date: January 2010
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: carboplatin
    Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29.
    Drug: Paclitaxel
    Paclitaxel 50 mg/m2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29.
    Other Name: taxol
    Drug: Panitumumab
    Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, prior to administration of chemotherapy at a dose of 6 mg/kg on day 1, 15 and 29.
    Other Name: Vectibix
    Radiation: 3-D conformal radiation
    A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy. All patients will be radiated by external beam radiation, using 3-D conformal radiation technique.
Detailed Description:

This is a Phase II, non-randomized trial. Eligible subjects will be treated with panitumumab plus carboplatin, paclitaxel and radiotherapy followed by surgical resection of the esophagus.

Panitumumab administration schedule: Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, prior to administration of chemotherapy at a dose of 6 mg/kg on day 1, 15 and 29. If the first infusion is well tolerated (without any serious infusion related reactions) all subsequent infusions may be administered over 30 minutes ± 10 minutes.

Chemotherapy regimen: Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29. Both drugs will be infused over one hour.

Radiotherapy treatment: A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy. All patients will be radiated by external beam radiation, using 3-D conformal radiation technique.

Surgery: Surgery will be performed preferably within 6 weeks after the completion of the chemoradiation and panitumumab. For carcinomas distal of the tracheal bifurcation but proximal to the gastro-esophageal junction, a transthoracic approach is preferred. For distal tumors involving the gastro-esophageal junction a transhiatal esophageal resection is preferred. A wide local excision including the N1 lymph nodes is carried out in both techniques including a standard excision of the lymph nodes around the coeliac axis. The continuity of the digestive tract will be restored by a gastric tube reconstruction or colonic interposition procedure with an anastomosis in the neck.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the intrathoracic esophagus or gastro esophageal junction
  • Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen.
  • T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible
  • Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm
  • If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach. Gastric cancers with minor involvement of the GE junction or distal esophagus are not eligible
  • No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula
  • Non pregnant, non-lactating female patients, not planning to become pregnant within 6 months after the end of treatment.
  • Age ≥ 18 and ≤ 75
  • ECOG performance status 0 or 1
  • Adequate hematological, renal, hepatic and pulmonary functions
  • Written, voluntary informed consent
  • Patients must be accessible to follow up and management in the treatment center

Exclusion Criteria:

  • Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment
  • Pregnancy (positive serum pregnancy test) and lactation
  • Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment
  • Previous chemotherapy, radiotherapy, treatment with an anti-EGFR antibody or with small molecule EGFR inhibitors
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization
  • Pulmonary fibrosis
  • Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
  • Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
  • Dementia or altered mental status that would prohibit the understanding and giving of informed consent
  • Inadequate caloric- and/or fluid intake
  • Weight loss > 15%.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01077999

Contacts
Contact: Hanneke Wilmink, MD PhD +31-20-5665955 j.w.wilmink@amc.uva.nl
Contact: Dick Richel, MD PhD +31-20-5665955 d.j.richel@amc.uva.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Hanneke Wilmink, MD PhD    +31-20-5665955    j.w.wilmink@amc.uva.nl   
Principal Investigator: Hanneke Wilmink, MD PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Hanneke Wilmink, MD PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided

Responsible Party: J.W. Wilmink, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01077999     History of Changes
Other Study ID Numbers: AMCmedon08/381
Study First Received: February 25, 2010
Last Updated: September 7, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
chemoradiation
panitumumab
esophageal cancer
Resectable squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the intrathoracic esophagus or gastro esophageal junction

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Carboplatin
Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014