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

NCT01627379 | Terminated Phase 3 DMC

• 2 other identifiers: POWER / AIO-STO-03092010-020606-15
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Squamous Cell Cancer

Keywords

nonresectable; advanced; metastatic esophageal squamous cell cancer; Panitumumab

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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.

  3 years

Secondary Outcomes (5)

• Progression-free survival

  every 9 weeks from Cycle 1 up to 3 years

• 1-year survival

  1 year

• Response rate

  every 9 weeks from Cycle 1 up to 3 years

• Overall incidence of patients with adverse events

  up to 3 years

• Quality of life

  every 3 weeks for up to 3 years

Study Arms (2)

Arm A: Cisplatin, 5-Fluorouracil

ACTIVE COMPARATOR

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

Drug: Cisplatin, 5-FU

Arm B: Cisplatin, 5-Fluorouracil and Panitumumab

EXPERIMENTAL

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

Drug: Panitumumab

Interventions

Cisplatin, 5-FU DRUG

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.

Arm A: Cisplatin, 5-Fluorouracil

Panitumumab DRUG

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.

Arm B: Cisplatin, 5-Fluorouracil and Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female ≥18 years of age
• Histologically proven squamous cell carcinoma of the esophagus, which is not curatively resectable\* or locally recurrent disease and both not eligible\*\* for definitive radiochemotherapy, or clearly metastatic disease (Tx, Nx, M1, locally unresectable T4, Nx, M0 or TX, N3, M0)\* or residual (post-resection) disease not eligible\*\* for definitive radiochemotherapy
• 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.
• Measurable or non-measurable disease according to RECIST 1.1
• ECOG 0-1
• Women of child-bearing potential must have a negative pregnancy test
• Laboratory requirements
• Hematology:
• Absolute neutrophil count ≥1.5x10\^9/L
• Platelet count ≥100x10\^9/L
• Leukocyte count ≥ 3.0x10\^9/L

You may not qualify if:

• Previous chemotherapy of esophageal cancer in the metastatic setting. Previous neoadjuvant chemotherapy or definitive radiochemotherapy with a maximum cumulative dose of 120 mg cisplatin and without recurrence of disease within 4 months after the end of treatment is allowed.
• 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.
• Previous exposure to EGFR-targeted therapy
• 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
• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
• 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.
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment
• 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.
• Hearing loss ≥ NCI-CTC V.4.03 Grade 3
• 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.
• Contraindications to receive any platin, 5-FU or panitumumab
• Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
• Known drug abuse/alcohol abuse
• Peripheral polyneuropathy ≥ NCI-CTC V 4.03 Grade 2

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Amgen: collaborator
• Assign Data Management and Biostatistics GmbH: collaborator
• Assign Clinical Research GmbH: collaborator

Study Sites (1)

Johannes-Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik

Mainz, Rhineland-Palatinate, 55101, Germany

Location

Related Publications (5)

• Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.

  PMID: 18784101 BACKGROUND

• Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Muller L, Rothling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. doi: 10.1093/annonc/mdp069. Epub 2009 Jun 23.

  PMID: 19549707 BACKGROUND

• Homs MY, v d Gaast A, Siersema PD, Steyerberg EW, Kuipers EJ. Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004063. doi: 10.1002/14651858.CD004063.pub2.

  PMID: 17054195 BACKGROUND

• Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1727-33. doi: 10.1016/S0140-6736(02)08651-8.

  PMID: 12049861 BACKGROUND

• Moehler M, Maderer A, Thuss-Patience PC, Brenner B, Meiler J, Ettrich TJ, Hofheinz RD, Al-Batran SE, Vogel A, Mueller L, Lutz MP, Lordick F, Alsina M, Borchert K, Greil R, Eisterer W, Schad A, Slotta-Huspenina J, Van Cutsem E, Lorenzen S. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Ann Oncol. 2020 Feb;31(2):228-235. doi: 10.1016/j.annonc.2019.10.018. Epub 2019 Dec 16.

  PMID: 31959339 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Cisplatin; Fluorouracil; Panitumumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Markus Möhler, PD Dr.

  I. Medizinische KLinik und Poliklinik, Johannes-Gutenberg-Universität Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2012
• First Posted: June 25, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2017
• Last Updated: March 2, 2018

Record last verified: 2018-03

Locations

DE (1)