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A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus

Phase 2
18 Years
70 Years
Not Enrolling
Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus

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Trial Information

A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus

A complete response rate of approximately 30% is achieved for standard treatment of
irresectable carcinoma of the oesophagus, consisting of concurrent chemoradiation therapy
(50.5 Gy + cisplatin/5-FU). Attempts to improve outcome by intensifying conventional
cytotoxic drugs or increasing the radiation dose have not been successful. Future
improvements will likely require the incorporation of targeted agents that probably will not
add significant toxicity, the use of molecular predictors of response and early
identification of responders. In both squamous cell carcinoma and adenocarcinoma of the
oesophagus expression of EGFR is correlated with poor outcome. Furthermore the addition of
cetuximab, a chimaeric EGFR antibody, to radiation therapy in head and neck cancer and
non-small cell lung cancer showed a gain in overall survival. In head and neck cancer
studies with the addition of panitumumab to chemo-radiation therapy are currently ongoing.
Therefore, we propose to perform a randomised phase II study of chemo-radiation therapy with
or without the combination of panitumumab (human EGFR antibody) in irresectable squamous
cell carcinoma or adenocarcinoma of the oesophagus without distant metastases.

Inclusion Criteria:

- Age 18 - 70years

- Histology proven SCC or adenocarcinoma of the oesophagus

- No proven (distant) metastases (ultrasonography, CT or MRI)

- No prior treatment for carcinoma of the oesophagus

- Karnofsky performance status ≥70% (appendix A)

- Irresectable disease as assessed by the multidisciplinary tumour board

- All patients (male and female) must use effective contraception methods according to
CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined
oral contraceptives, IUDs, sexual abstinence or vasectomised partner), for the whole
duration of the study and until six months after they received the last treatment

- No contraindications for cytotoxic therapy or panitumumab:

- No known hypersensitivity/allergy to any of the compounds used

- Haematology: Neutrophil count ≥ 1.5∙109 /L Thrombocyte count ≥ 100∙109 /L Haemoglobin
≥ 6.2 mmol/L (100 g/L)

- No known HIV infection or other condition of persistent immunodeficiency

- Renal function:

- Creatinine clearance (MDRD) ≥ 60 mL/min

- Hepatic function:

- Total bilirubin ≤ 1.5∙ULN

- AST, ALT, AP ≤ 2.5∙ULN

- Electrolyte balance:

- (albumin corrected) calcium ≤ 2.87 mmol/L (=11.5 mg/dl) but ≥ lower limit of normal

- Magnesium ≥ LLN

- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan.

- No known other serious illness or medical condition present at entry in the study
including: Unstable cardiac disease despite treatment, congestive heart failure NYHA
grade 3 and 4 Clinically significantly abnormal electrocardiogram (ECG) or left
ventricular ejection fraction (LVEF) below the institutional ULN

- Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) ≤ 1 year before enrolment/randomisation

- Significant neurologic or psychiatric disorders

- Active uncontrolled infection Active disseminated intravasal coagulation

- Symptomatic peripheral neuropathy (CTCAE v3.0 term "neuropathy: sensory") ≥ grade 2
Ototoxicity (CTCAE v3.0 any term in "auditory/ear") ≥ grade 2 except if due to trauma
or mechanical impairment due to tumour mass

- Other serious underlying medical condition which could impair the ability of the
patient to participate in the study No or insufficient oral nutrient intake

- No prior exposure to EGFR pathway targeting agents

- No known drug abuse

- Absence of any psychological, familial, sociological (e.g. severe alcohol addiction
expected to hamper protocol compliance) or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with the patient before registration in the trial

- No participation in another interventional clinical trial in the preceding 30 days

- Written informed consent to participate to study must be given according to ICH/GCP,
and national/local regulations.

Exclusion Criteria:

- Prior treatment for this tumour

- Prior treatment with radiation therapy in the area of the oesophagus or other site
that will interfere with proposed treatment

- Subject pregnant or breast feeding, or planning to become pregnant within 6 months
after the end of treatment.

- Subject (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.

- History of other prior malignancy in past 5 years, other than basal cell carcinoma,
squamous cell carcinoma of the skin, or cervical carcinoma in situ.

Exclusion criteria for the PET-scan (secondary endpoint)

For the PET-scan the following exclusion criteria are used:

- Severe claustrophobia

- Diabetes mellitus (type I and II)

- Serum glucose level >11 mmol/L

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

1-year overall survival

Outcome Description:

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.

Outcome Time Frame:


Safety Issue:


Principal Investigator

C.M.L. van Herpen, Md PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Medical Centre Nijmegen


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

January 2011

Completion Date:

October 2012

Related Keywords:

  • Irresectable Squamous Cell or Adenocarcinoma of the Oesophagus
  • oesophagus cancer
  • chemoradiotherapy
  • panitumumab
  • irresectable
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell