Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Cisplatin

Panitumumab

Antineoplastic Agents, Immunological

Chemotherapy will be administered every 3 weeks until progression of disease or any other reason for treatment withdrawal is fulfilled.

Chemotherapy plus Panitumumab will be administered every 3 weeks until progression of disease or any other reason for treatment withdrawal is fulfilled.

Arm A: Cisplatin 80 mg/m2 IV infusion over 2 hours on Day 1, followed by 5-FU 1000 mg/m2 IV daily as continuous infusion over 24 hours, Day 1-4.

Chemotherapy will be administered every 3 weeks until progression of disease or any other reason for treatment withdrawal is fulfilled.

Cisplatin, 5-FU

Arm B: Cisplatin 80 mg/m2 IV infusion over 2 hours on Day 1, followed by 5-FU 1000 mg/m2 IV daily as continuous infusion over 24 hours, Day 1-4.

Panitumumab will be administered on Day 1 of each treatment cycle at a dose of 9 mg/kg prior to administration of chemotherapy.

Each treatment cycle is defined as 21 days. Patients are treated until progression of disease occurs or any other reason for treatment withdrawal is fulfilled.

Markus Möhler, PD Dr.

More than 50% of patients with esophageal cancer have locally advanced or metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival.

Previous data suggested not only that EGFR antibody targeted therapy may be safely combined with cisplatin and 5-FU but also may increase the efficacy of standard cisplatin / 5-FU regime.

In the present study, patients with nonresectable, advanced or metastatic esophageal squamous cell cancer (ESCC) will receive chemotherapy or chemotherapy plus panitumumab every 3 weeks until disease progression occurs.

The primary objective is to demonstrate superiority of 5-FU, Cisplatin and Panitumumab over 5-FU and Cisplatin alone in terms of overall survival in esophageal cancer.

More than 50% of patients with esophageal cancer have locally advanced or metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival. The most frequently used agents are 5-fluorouracil, cisplatin, with or without various anthracyclines. Cisplatin plus continuous 5-fluorouracil are the standard of care regimens. Taxanes and anthracyclins are eligible agents for possible future studies, however with higher incidences of toxicities and life threatening complications. Response rates for single agents range from 15%-30%. Combination regimens usually tend to produce higher response rates and occasionally patients achieve complete responses (0%-11%). However, with the combination regimens, the median survival time remains clearly less than 10 months, mostly between 4-8 months \[Homs MY et al\]. In comparison of different chemotherapy protocols, there was no consistent benefit of any specific chemotherapy regimen. So far, cisplatin combined with 5-fluorouracil is one of the approved standard regimens in esophageal cancer world wide\[Medical Research Council Oesophageal Cancer Group\]. This so called three-weekly MRC regimen has a better toxicity profile than the four weekly CF regimen given in Central Europe with the higher Cisplatin dose\[Lorenzen S et al\], but less overall chemotherapy given per 4 months.

Advances in molecular biology and new molecular technologies can possibly contribute to improvement of response to neoadjuvant or palliative therapy in ESCC patients as well. EGFR1 blockade with platinum-based chemotherapy already significantly improved response rates as well as the progression-free and overall survival compared to chemotherapy alone in patients with head and neck tumors, which are also squamous cancers\[Vermorken JB et al\].

Even more, the Arbeitsgemeinschaft Internistische Onkologie (AIO) has performed a randomized phase II study of the EGFR antibody cetuximab plus cisplatin/5-fluorouracil versus cisplatin/5-fluorouracil alone in first-line metastatic ESCC\[Lorenzen S et al\]. For a maximum of six 28-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2) days 1-5 (CF), either alone or in combination with cetuximab (CET-CF). The primary endpoint was tumor response. From 62 eligible patients included, 32 receiving CET-CF and 30 CF. Cetuximab weekly did not exacerbate grade 3/4 toxicity, except for rash (6% vs 0%) and diarrhea (16% vs 0%). The overall response rate according to RECIST criteria were 19% and 13% and the disease control rates, were 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in the 37 evaluated samples.

Thus, with respect to the AIO data and in concordance with the head and neck data by Vermorken, EGFR antibody targeted therapy may not only be safely combined with CF, but may also very likely increase the efficacy of standard CF, particularly with regard to a chosen primary endpoint of overall survival. Therefore, the aim of this study is to investigate if the overall survival of patients with squamous cell carcinoma of the esophagus can be prolonged if panitumumab is added to the standard CF chemotherapy.

Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable,Advanced or Metastatic Esophageal Squamous Cell Cancer

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

Kaplan-Meier estimate of the median time between date of randomization and the date of death from any cause or the date of last follow-up in case of no documentation of death.

Comparison of Overall survival of treatment arms "Panitumumab + Chemotherapy" and "Chemotherapy only" in patients with nonresectable, advanced or metastatic ESCC.

Kaplan-Meier estimate of the median time span between the date of randomization and the date of progression or death due to any cause.

The difference in progression-free survival between the two treatment arms will be tested.

Tumor assessments will be performed every 9 weeks during the treatment period.

The difference in 1-year survival between the two treatment arms is determined.

Best objective response is defined as the best response documented during study. To compare objective response rate between the two treatment arms.

Tumor Assessments will be performed every 9 weeks during the treatment period.

Throughout the treatment period until the End of treatment visit, patients will be assessed for all adverse events. CTCAE V 4.03 will be used for grading.

Spots Global Cancer Trial Database for nonresectable