Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

NCT02083653 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: Sym004-052013-003829-29EMR200637-002
• Study Type: interventional
• Target: 254
• Locations: 10 countries
• Sites: 54

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).

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; Best Supportive Care; Capecitabine; Fluorouracil (5-FU); Sym004

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) Time

  OS based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley. If a subject had not died, survival time was censored at the last date the subject was known to be alive.

  From randomization until the date of death (assessed up to 32 months).

Secondary Outcomes (11)

• Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

  From randomization until first radiological confirmed or clinical progression event, or death due to any cause, within 12 weeks after last tumor assessment (assessed up to 32 months).

• Progression Free Survival (PFS) Time

  From randomization until first event, where an event can be a progression (radiological confirmed or clinical progression) or death due to any cause (assessed up to 32 months).

• Time to Treatment Failure (TTF)

  From randomization until treatment discontinuation for any reason, including disease progression or death (assessed up to 32 months).

• Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03).

  From Baseline up to 28 days after the last IMP administration.

• Relative Dose Intensity of Sym004

  From first dose of study drug until disease progression (assessed up to 32 months).

Study Arms (3)

Arm A: Sym004 (12 mg/kg)

EXPERIMENTAL

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.

Drug: Sym004 (12 mg/kg)

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

EXPERIMENTAL

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.

Drug: Sym004 (9/6 mg/kg)

Arm C: Investigator's Choice

ACTIVE COMPARATOR

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

Other: Best Supportive Care (BSC); Drug: Fluorouracil (5-FU); Drug: Capecitabine

Interventions

Sym004 (12 mg/kg) DRUG

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

Arm A: Sym004 (12 mg/kg)

Sym004 (9/6 mg/kg) 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)

Best Supportive Care (BSC) 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.

Arm C: Investigator's Choice

Fluorouracil (5-FU) DRUG

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

Also known as: Adrucil

Arm C: Investigator's Choice

Capecitabine DRUG

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

Also known as: Xeloda

Arm C: Investigator's Choice

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (54)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Florida Cancer Specialists-Broadway

Fort Myers, Florida, 33916, United States

Location

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Mercy Research

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

SMZ Süd - Kaiser Franz Josef Spital Wien

Vienna, 1100, Austria

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

Clinique et Maternité Sainte-Elisabeth

Namur, 5000, Belgium

Location

CHU Mont-Godinne

Yvoir, 5530, Belgium

Location

ICO - Site Paul Papin

Angers, 49933, France

Location

Institut Sainte Catherine

Avignon, 84000, France

Location

Groupe Hospitalier Saint André - Hôpital Saint André

Bordeaux, 33075, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

CRLCC Eugene Marquis

Rennes, 35042, France

Location

ICO - Site René Gauducheau

Saint-Herblain, 44805, France

Location

CHU de Toulouse - Hôpital Rangueil

Toulouse, 31059, France

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, 60590, Germany

Location

Uzsoki Utcai Korhaz

Budapest, 1145, Hungary

Location

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, 3526, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Korhaz-Rendelointezet

Szolnok, 5000, Hungary

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti

Ancona, 60126, Italy

Location

Azienda Ospedaliero Universitaria San Martino

Genova, 16132, Italy

Location

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Milan, 20162, Italy

Location

Seconda Università degli Studi di Napoli

Napoli, 80138, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Presidio Ospedaliero SS. Trinità Sora

Sora, 03039, Italy

Location

Azienda Ospedaliera S. Maria Di Terni

Terni, 05100, Italy

Location

SPZOZ MSW zWarmińsko-MazurskimCen.Onko.wOlsztynie

Olsztyn, 10-228, Poland

Location

Wielkopolskie Centrum Onkologii

Poznan, 61-866, Poland

Location

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, 87-100, Poland

Location

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, 02-781, Poland

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, 644013, Russia

Location

St. Petersburg SHI "City Clinical Oncology Dispensary"

Saint Petersburg, 197022, Russia

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

ICO l´Hospitalet - Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Related Publications (2)

• 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.

  PMID: 8433390 BACKGROUND

• 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.

  BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

futuximab; Fluorouracil; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Considering the hypothesis-generating nature of a phase 2 clinical trial, the intent-to-treat (ITT) analysis should be viewed as the starting point of a scientific investigation process, not the final conclusion.

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Symphogen A/S

info@symphogen.com

+45 8838 2600

Study Officials

• Josep Tabernero, MD, PhD

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 11, 2014
• Study Start: March 6, 2014
• Primary Completion: October 24, 2016
• Study Completion: April 26, 2017
• Last Updated: April 16, 2019
• Results First Posted: December 24, 2018

Record last verified: 2019-04

Locations

IT (9); FR (8); ES (8); AU (1); RU (2); US (9); HU (4); PL (4); BE (7); DE (2)