An open-label, randomized phase III trial of cisplatin and 5-fluorouracil with or without panitumumab for patients with nonresectable, advanced or metastatic esophageal squamous cell cancer

• Conditions: Patients with nonresectable, advanced or metastatic esophageal squamous cell cancer (ESCC); MedDRA version: 14.1Level: LLTClassification code 10015363Term: Esophageal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10062478Term: Esophageal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10055102Term: Oesophageal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10030152Term: Oesophageal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-020606-15-BE
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-29
• Last Update Posted: 17 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1.Signed written informed consent
2.Male or female =18 years of age
3.Histologically proven squamous cell carcinoma of the esophagus, which is not curatively respectable* and not eligible for definitive radiochemotherapy**. Patients with locally recurrent disease or clearly metastatic disease (Tx, Nx, M1, locally unresectable T4, Nx, M0 or TX, N3, M0) or macroscopically residual (post-resection) disease not eligible for definitive radiochemotherapy may be enrolled.
*resectability has to be defined prior to randomization according to local standards:
The tumor is considered unresectable due to:
T-stage, N-stage, performance status/nutritional status, co-morbidity (pulmonary function, other), tumor location upper third of the esophagus, relation to other organs/structures), patient refusal, other reasons.
**eligibility to definitive radiochemotherapy will be determined according to local standards based on the extent of disease, performance status/nutritional status, co-morbidity (pulmonary function, other), volume of neighboring organs within the radiation field, patient refusal, other reasons.
4.Measurable or non-measurable disease according to RECIST 1.1
5.ECOG 0-1
6.Women of child-bearing potential must have a negative pregnancy test
7.Laboratory requirements
•Hematology:
oAbsolute neutrophil count =1.5x109/L
oPlatelet count =100x109/L
oLeukocyte count > 3.0x109/L
oHemoglobin = 9 g/dL or 5.59 mmol/l
•Hepatic Function:
oTotal bilirubin = 1.5 time the upper normal limit (UNL)
oAST = 2.5xUNL in absence of liver metastases, or =5xUNL in presence of liver metastases
oALT = 2.5xUNL in absence of liver metastases, or =5xUNL in presence of liver metastases
•Renal Function:
oCreatinine clearance =50 mL/min according to Cockroft-Gault formula
•Metabolic Function
oMagnesium = 0,5 mmol/l or 1,2 mg/dL
oCalcium = 2 mmol/L or 8.0 mg/dL
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1.Previous chemotherapy of esophageal cancer except for neoadjuvant treatment with a maximum cumulative dose of 120 mg cisplatin and without recurrence within 4 months after the end of treatment.
2.Concurrent radiotherapy involving target lesions used for this study. Concurrent palliative radiation for non-target lesions is allowed if other lesions are available outside the involved field. Previous pre-operative or post-operative radiotherapy is allowed.
3.Previous exposure to EGFR-targeted therapy
4.Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
5.Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
6.Serious concomitant disease or medical condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduces the probability of assessing clinical effect.
7.Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ? 1 year before enrolment
8.Inadequate pulmonary function according to the Investigator’s judgment, history of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
9.Hearing loss > NCI-CTC V.4.0.3 Grade 3
10.Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
11.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.
12.Contraindications to receive any platin, 5-FU or panitumumab
13.Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
14.Current drug abuse/alcohol abuse interferring with compliance with the study requirements
15.peripheral polyneuropathy > NCI-CTC V 4.03 Grade 2
16.chronic inflammatory bowels diseases
17.Social situations limiting the compliance with the study requirements
18. History of HIV infection or chronic hepatitis B or C
19. Concurrent treatment with brivudin or sorivudin or its chemically related analogues.
There must be at least a 4-week wash-out period between end of treatment with brivudin,
sorivudin or its chemically related analouges and start of therapy with 5-FU.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified