Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

NCT ID: NCT02083653

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-06
• Study Completion Date: 2017-04-26

Brief Summary

This is a Phase 2, open-label, randomized, 3-arm trial investigating the efficacy of two Sym004 doses (Arm A and Arm B) compared with a control group (Arm C) in subjects with metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs).

Detailed Description

This trial assesses the efficacy of two different weekly dosing regimens of Sym004 (Arm A: 12 mg/kg/week versus Arm B: 9 mg/kg loading dose followed by 6 mg/kg/week) compared with investigator's choice in terms of overall survival time in subjects with mCRC. Subjects assigned to Arm C will receive best supportive care (BSC), Fluorouracil (5-FU), or Capecitabine, per local standard of care.

Subjects will receive treatment until unacceptable toxicity, disease progression, withdrawal of consent, or until the subject meets any of the criteria for treatment discontinuation or trial discontinuation. Therefore, the duration of treatment will differ among individuals and cannot be fixed in advance.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Sym004 (12 mg/kg)

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Group Type: EXPERIMENTAL

Sym004 (12 mg/kg)

Intervention Type: DRUG

Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Arm B: Sym004 (9/6 mg/kg)

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Group Type: EXPERIMENTAL

Sym004 (9/6 mg/kg)

Intervention Type: DRUG

Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Arm C: Investigator's Choice

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Group Type: ACTIVE_COMPARATOR

Best Supportive Care (BSC)

Intervention Type: OTHER

BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU)

Intervention Type: DRUG

5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Interventions

Sym004 (12 mg/kg)

Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Intervention Type: DRUG

Sym004 (9/6 mg/kg)

Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Intervention Type: DRUG

Best Supportive Care (BSC)

BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Intervention Type: OTHER

Fluorouracil (5-FU)

5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Intervention Type: DRUG

Capecitabine

Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Intervention Type: DRUG

Other Intervention Names

Adrucil; Xeloda

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained before undergoing any study-related activities
• Male or female, at least 18 years of age
• Subjects with histologically or cytologically confirmed mCRC, Kirsten rat sarcoma wild-type (KRAS WT) at initial diagnosis
• Failure of or intolerance to 5-FU, Oxaliplatin, and Irinotecan
• Acquired resistance to marketed anti-EGFR mAbs as defined in the protocol
• Measurable disease defined as one or more target lesions according to RECIST
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

Exclusion Criteria

• Pretreatment with regorafenib.
• Subjects who in the opinion of the subject and investigator would benefit more from regorafenib treatment (except where regorafenib is not reimbursed in the country)
• Skin rash Common Terminology Criteria for AEs (CTCAE) Grade greater than 1 from previous anti-EGFR therapy at time of randomization
• Magnesium less than 0.9 milligram per deciliter (mg/dL)
• Known hypersensitivity to any of the treatment ingredients. Known previous Grade 3-4 infusion related reactions with anti-EGFR mABs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Symphogen A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josep Tabernero, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vall d'Hebron University Hospital

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Sharp Memorial Hospital

San Diego, California, United States

Florida Cancer Specialists-Broadway

Fort Myers, Florida, United States

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, United States

Florida Cancer Specialists

St. Petersburg, Florida, United States

Mercy Research

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Texas Oncology, P.A.

Tyler, Texas, United States

SMZ Süd - Kaiser Franz Josef Spital Wien

Vienna, , Austria

ULB Hôpital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

CHU Ambroise Paré

Mons, , Belgium

Clinique et Maternité Sainte-Elisabeth

Namur, , Belgium

CHU Mont-Godinne

Yvoir, , Belgium

ICO - Site Paul Papin

Angers, , France

Institut Sainte Catherine

Avignon, , France

Groupe Hospitalier Saint André - Hôpital Saint André

Bordeaux, , France

Centre Georges François Leclerc

Dijon, , France

Centre Léon Bérard

Lyon, , France

CRLCC Eugene Marquis

Rennes, , France

ICO - Site René Gauducheau

Saint-Herblain, , France

CHU de Toulouse - Hôpital Rangueil

Toulouse, , France

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, , Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, , Germany

Uzsoki Utcai Korhaz

Budapest, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

Jasz-Nagykun-Szolnok Megyei Korhaz-Rendelointezet

Szolnok, , Hungary

Azienda Ospedaliero Universitaria Ospedali Riuniti

Ancona, , Italy

Azienda Ospedaliero Universitaria San Martino

Genova, , Italy

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Milan, , Italy

Seconda Università degli Studi di Napoli

Napoli, , Italy

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Presidio Ospedaliero SS. Trinità Sora

Sora, , Italy

Azienda Ospedaliera S. Maria Di Terni

Terni, , Italy

SPZOZ MSW zWarmińsko-MazurskimCen.Onko.wOlsztynie

Olsztyn, , Poland

Wielkopolskie Centrum Onkologii

Poznan, , Poland

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, , Poland

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, , Poland

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, , Russia

St. Petersburg SHI "City Clinical Oncology Dispensary"

Saint Petersburg, , Russia

Hospital del Mar

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

ICO l´Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Countries

United States; Austria; Belgium; France; Germany; Hungary; Italy; Poland; Russia; Spain

References

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.

Reference Type: BACKGROUND

PMID: 8433390 (View on PubMed)

Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published by: European Organisation for Research and Treatment of Cancer, Brussels 2001.

Reference Type: BACKGROUND

Other Identifiers

2013-003829-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR200637-002

Identifier Type: OTHER

Identifier Source: secondary_id

Sym004-05

Identifier Type: -

Identifier Source: org_study_id