Clinical trial NCT02083653: Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer
Official title: Open-label, Randomized, Controlled, Multicenter Phase II Trial Investigating 2 Sym004 Doses Versus Investigator's Choice (Best Supportive Care, Capecitabine, 5-FU) in Subjects With Metastatic Colorectal Cancer and Acquired Resistance to Anti-EGFR Monoclonal Antibodies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
Best Supportive Care
Capecitabine
Fluorouracil (5-FU)
Sym004
Lead sponsor: Symphogen A/S
Sponsor class: INDUSTRY
First posted: 2014-03-11
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* Other protocol defined inclusion criteria could apply

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
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Overall Survival (OS) Time
timeFrame: From randomization until the date of death (assessed up to 32 months).
Secondary outcomes:
measure: Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: 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).
measure: Progression Free Survival (PFS) Time
timeFrame: 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).
measure: Time to Treatment Failure (TTF)
timeFrame: From randomization until treatment discontinuation for any reason, including disease progression or death (assessed up to 32 months).
measure: Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03).
timeFrame: From Baseline up to 28 days after the last IMP administration.
measure: Relative Dose Intensity of Sym004
timeFrame: From first dose of study drug until disease progression (assessed up to 32 months).
measure: Pharmacokinetic (PK) Parameters: Sym004 Concentrations
timeFrame: Weeks 3, 5, and 7 and at the End of Treatment visit, including a Week 1 and Week 2 subset.
measure: Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax)
timeFrame: Day 1 on Weeks 1-3 followed by Week 5 Day 1 and Week 7 Day 1.
measure: Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time
timeFrame: Every two weeks (Days 15, 29, and 43) followed by every six weeks thereafter (Days 78, 120, 162, etc.) until the End of Treatment Visit
measure: Quality of Life Assessed by the EORTC QLQ-C30 (Version 3)
timeFrame: Assessed every 6 weeks (week 1 and week 7 reported)
measure: Quality of Life Assessed by EORTC QLQ-CR29
timeFrame: Assessed every 6 weeks (week 1 and week 7 reported)
measure: Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash
timeFrame: Assessed every 3 weeks (week 1 and week 4 reported)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-Broadway
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology - Oncology Associates of Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Research
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Tyler
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Wien
country: Austria
facility: SMZ Süd - Kaiser Franz Josef Spital Wien
city: Bruxelles
country: Belgium
facility: ULB Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte-Elisabeth
city: Yvoir
country: Belgium
facility: CHU Mont-Godinne
city: Angers Cedex 9
country: France
facility: ICO - Site Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux Cedex
country: France
facility: Groupe Hospitalier Saint André - Hôpital Saint André
city: Dijon Cedex
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Rennes Cedex
country: France
facility: CRLCC Eugene Marquis
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse - Hôpital Rangueil
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
city: Nyiregyhaza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Korhaz-Rendelointezet
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale Niguarda Ca' Granda
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Sora
country: Italy
facility: Presidio Ospedaliero SS. Trinità Sora
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria Di Terni
city: Olsztyn
country: Poland
facility: SPZOZ MSW zWarmińsko-MazurskimCen.Onko.wOlsztynie
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg SHI "City Clinical Oncology Dispensary"
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Vall d'Hebron University Hospital
name: Josep Tabernero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.