Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus (PANORAMIC)
For esophageal cancer that can not be removed by surgery, the choice of treatment is a combination of chemotherapy and radiotherapy. We call this combination- (or concurrent) chemoradiotherapy. Chemotherapy is treatment with drugs that kill cancer cells. Both chemotherapy and radiotherapy make the tumour smaller and enhance each other's effect. The goal of treatment with chemotherapy and radiation therapy is to cure the cancer. Unfortunately only a small proportion of patients are cured with this treatment.
Improvements in the outcome of treatment may be expected by using the so-called "targeted" treatments. With esophageal cancer, a protein (the epidermal growth factor receptor (this is a kind of trap), the EGFR), is present in many tumours. This protein causes the tumor to grow. Panitumumab is a drug that blocks the functioning of this receptor (catcher), so that possibly the growth and spread of esophageal cancer is prevented.
The main objective of this trial is to see if survival of patients with inoperable esophageal cancer improves as panitumumab is added to standard treatment with chemoradiotherapy.
It will also investigate whether patients tolerate the addition of panitumumab to the standard treatment. Also, the biological characteristics of the tumor will be examined. In a proportion of patients it will be determined how the enhancement of the cancer is visible on an FDG-PET scan before the start of treatment and how this changes during the treatment. It will be also be evaluated how this treatment affects the survival.
|Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus||Drug: CRT + Panitumumab Drug: Concurrent chemoradiation therapy without panitumumab||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus|
- 1-year overall survival [ Time Frame: 1-year ]To describe the 1-year OS rate after concurrent CRT with or without panitumumab in irresectable carcinoma of the oesophagus. The control arm is used to validate whether the historical cohort used for comparison is similar to our success-rate.
- toxicity [ Time Frame: during treatment and follow up ]Investigation of the acute and long-term toxicity of both study arms (according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0);
- PFS [ Time Frame: between randomisation and date of PD ]PFS: interval between randomisation date and the date at which disease progression is established being not suspicious for a second cancer (histologically confirmed when in doubt) or date of death from any cause but clearly not related to disease- or treatment (e.g. accident). Patients still disease-free after 18 months follow-up or lost to follow-up or death clearly not related to disease or treatment (e.g. accident)), are censored at the date of the most recent follow-up or at the analysis cut-off date, whichever comes first.
- Response Rate [ Time Frame: 3 months after treatment ]Response rate: partial (PR) or complete response (CR) according to RECIST 1.1 at 3 months after treatment
- pharmacodynamics of panitumumab [ Time Frame: biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy ]pharmacodynamics (PD) of panitumumab (EGFR, K-RAS, B-RAF, downstream signalling pathways ) compared between the biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy
- Quantification of baseline FDG uptake (SUV) with PET, and SUV changes [ Time Frame: baseline 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks. ]
baseline, 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks.
2-4 weeks after finishing treatment. 10-12 weeks after finishing treatment
- CTCs and CECs [ Time Frame: baseline,after 2 weeks during chemo-radiation therapy and 12 weeks after finishing treatment ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||October 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
|Experimental: Concurrent chemoradiation therapy with panitumumab||
Drug: CRT + Panitumumab
Day -7, day +15 and day +36: panitumumab 9.0 mg/kg i.v. Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.
|Active Comparator: Concurrent chemoradiation therapy without panitumumab||
Drug: Concurrent chemoradiation therapy without panitumumab
Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01262183
|University Medical Centre Nijmegen|
|Nijmegen, Gelderland, Netherlands, 6500 HB|
|Principal Investigator:||C.M.L. van Herpen, Md PhD||University Medical Centre Nijmegen|