ECX + Panitumumab vs. ECX Alone in Locally Advanced Gastric Cancer or Cancer of the Gastroesophageal Junction

NCT01234324 | Completed Phase 2 DMC

• 2 other identifiers: AIO/CAO-STO-08012008-007798-18
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 1

Brief Summary

That panitumumab in combination with Epirubicin, Cisplatin and Capecitabine (ECX) will safely decrease the frequency of pT3/T4 below that of ECX alone in subjects with locally advanced adenocarcinoma of the stomach and gastroesophageal junction.

Conditions

Stomach Neoplasms; Gastroesophageal Junction Neoplasms

Keywords

Stomach Neoplasms; Gastroesophageal Junction Neoplasms; gastric cancer; cancer of the gastroesophageal junction

Outcome Measures

Primary Outcomes (1)

• Frequency of pT3/T4 categories after surgery

  after 9 weeks treatment

Secondary Outcomes (1)

• Frequencies of pN2/N3 categories after surgery

  After 9 weeks treatment

Study Arms (2)

Arm 1: ECX + Panitumumab

EXPERIMENTAL

Drug: Epirubicin, Cisplatin, Capecitabine, Panitumumab

Arm 2: EXC alone

ACTIVE COMPARATOR

Drug: Epirubicin, Cisplatin, Capecitabine

Interventions

Epirubicin, Cisplatin, Capecitabine, Panitumumab DRUG

Epirubicin: 50mg/m², administered as an intravenous bolus over 10min on day 1 of each 21 day cycle; Cisplatin: 60mg/m², administered as an intravenous infusion over 4h on day 1 of each 21 day cycle; Capecitabine: 625mg/m², administered orally twice daily on each day of each 21 day cycle; Panitumumab: 9 mg/kg bodyweight, administered IV by an infusion pump through a peripheral line or catheter over 60 min +-15 min on day 1 of each 21 day cycle. Number of Cycles: 3 neoadjuvant cycles and 3 adjuvant cycles until disease progression, withdrawal of consent or unacceptable toxicity develops.

Also known as: Xeloda®

Arm 1: ECX + Panitumumab

Epirubicin, Cisplatin, Capecitabine DRUG

Epirubicin: 50mg/m², administered as an intravenous bolus over 10min on day 1 of each 21 day cycle; Cisplatin: 60mg/m², administered as an intravenous infusion over 4h on day 1 of each 21 day cycle; Capecitabine: 625mg/m², administered orally twice daily on each day of each 21 day cycle. Number of Cycles: 3 neoadjuvant cycles and 3 adjuvant cycles until disease progression, withdrawal of consent or unacceptable toxicity develops.

Also known as: Vectibix®, Xeloda®

Arm 2: EXC alone

Eligibility Criteria

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

You may qualify if:

• Competent to comprehend, sign, and date an IEC-approved informed consent form, written informed consent.
• Of either gender and aged 18 years or more.
• Diagnosed with histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction of Type I/II/III according to the classification of Siewert et al, 1996.
• Stage uT/3 or 4 N0/+ and M0 disease evaluated by endoscopic ultrasound, spiral computed tomography of the chest, abdomen and pelvis and by laparoscopy in uT3/T4 tumors.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Leucocyte count \> 3,000/mm3.
• Platelet count ≥100,000/mm3.
• Haemoglobin ≥10 g/dl.
• Serum creatinine ≤ 1.5x of upper limit of normal (ULN).
• Creatinine clearance \> 60 ml/kg/min measured either by 24-h urine sampling or calculated by using the Cockcroft-Gault formula .
• Aspartate aminotransferase (AST) ≤3 x ULN.
• Alanine aminotransferase (ALT) ≤3 x ULN.
• Bilirubin ≤ 1.5 x ULN.
• Magnesium ≥ lower limit of normal.
• Calcium ≥ lower limit of normal.

You may not qualify if:

• Any metastatic disease.
• Other malignant tumours less than five years old. Exceptions include basocellular carcinoma, in situ cancer of the cervix of the uterus, or any curatively-treated other malignancies without evidence of disease for more than five years.
• Significant ascites or pleural effusion.
• Prior anti-EGFr antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib).
• Prior chemotherapy, radiotherapy or antibody therapy for gastric cancer or cancer of the gastro-oesophageal junction.
• Concomitant therapy with sorivudine or analogue compounds.
• Known previous or ongoing abuse of narcotic drug, other medication or alcohol.
• Significant cardiovascular disease including New York Heart Association (NYHA) grade II or greater congestive heart failure, peripheral arterial occlusive disease stage II or greater, symptomatic coronary heart disease, insufficiently treated arterial hypertension, unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
• History or evidence upon physical examination of CNS disease unless adequately treated, seizure not controlled with standard medical therapy, or history of stroke.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan.
• Pre-existing polyneuropathy grade \>1 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), except for loss of tendon reflex as the only symptom.
• Treatment for systemic infection within 14 days before initiating study treatment.
• Active inflammatory bowel disease, serious gastric ulceration or other bowel disease causing chronic diarrhoea (defined as \> 4 loose stools per day).
• Suspected or known dihydropyrimidine dehydrogenase deficiency (DPD).
• Thrombosis or severe bleeding within six months prior to entry into the study (except for bleeding of the tumour before its surgical resection), evidence of bleeding diathesis or coagulopathy, or current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants for therapeutic purposes.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Amgen: collaborator
• WiSP Wissenschaftlicher Service Pharma GmbH: collaborator

Study Sites (1)

AIO-Studien gGmbH

Berlin, 10623, Germany

Location

Related Publications (6)

• Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, Bottcher K, Siewert JR, Hofler H. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003 Oct 1;98(7):1521-30. doi: 10.1002/cncr.11660.

  PMID: 14508841 BACKGROUND

• Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.

  PMID: 16822992 BACKGROUND

• Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. doi: 10.1056/NEJMoa033025.

  PMID: 15269313 BACKGROUND

• Garcia I, del Casar JM, Corte MD, Allende MT, Garcia-Muniz JL, Vizoso F. Epidermal growth factor receptor and c-erbB-2 contents in unresectable (UICC R1 or R2) gastric cancer. Int J Biol Markers. 2003 Jul-Sep;18(3):200-6. doi: 10.1177/172460080301800308.

  PMID: 14535591 BACKGROUND

• Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. doi: 10.3322/canjclin.50.1.7.

  PMID: 10735013 BACKGROUND

• Stahl M, Maderer A, Lordick F, Mihaljevic AL, Kanzler S, Hoehler T, Thuss-Patience P, Monig S, Kunzmann V, Schroll S, Sandermann A, Tannapfel A, Meyer HJ, Schuhmacher C, Wilke H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) Oesophageal and Gastric Cancer Working Group and the Chirurgische Arbeitsgemeinschaft Onkologie (CAOGI/DGAV) of the German Cancer Society. Perioperative chemotherapy with or without epidermal growth factor receptor blockade in unselected patients with locally advanced oesophagogastric adenocarcinoma: Randomized phase II study with advanced biomarker program of the German Cancer Society (AIO/CAO STO-0801). Eur J Cancer. 2018 Apr;93:119-126. doi: 10.1016/j.ejca.2018.01.079. Epub 2018 Mar 20.

  PMID: 29501977 DERIVED

Related Links

• Arbeitsgemeinschaft der internistischen Onkologie

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Epirubicin; Cisplatin; Capecitabine; Panitumumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• M. Stahl, Prof. Dr. med.

  Klinken Essen-Mitte Evang. Huyssens-Stiftung

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2010
• First Posted: November 4, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2017
• Last Updated: January 23, 2018

Record last verified: 2018-01

Locations

DE (1)