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Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S
ClinicalTrials.gov Identifier:
NCT02083653
First received: March 7, 2014
Last updated: June 19, 2017
Last verified: June 2017
  Purpose
This is a Phase 2, open-label, 3-arm trial of two Sym004 doses (Arms A and B) and 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).

Condition Intervention Phase
Metastatic Colorectal Cancer Drug: Sym004 Other: Best supportive care (BSC) Drug: Fluorouracil (5-FU) Drug: Capecitabine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Symphogen A/S:

Primary Outcome Measures:
  • Overall survival (OS) Time [ Time Frame: Up to 2.5 years ]
    OS time is defined as the time from randomization to the date of death, assessed up to 2.5 years.


Secondary Outcome Measures:
  • Best overall response according to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: 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 2.5 years ]
  • Progression Free Survival (PFS) Time [ Time Frame: Time 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 2.5 years ]
  • Time to treatment failure [ Time Frame: Time from randomization to treatment failure or last tumor assessment, assessed up to 2.5 years ]
  • Relative dose intensity of Sym004 [ Time Frame: From first dose of study drug until unacceptable toxicity, disease progression, or consent withdrawal, assessed up to 2.5 years ]
  • Pharmacokinetic parameters: AUC (0-168 hours), t1/2, CL, Vd, Cmax, tmax and C(trough) [ Time Frame: Up to Year 2.5 ]
  • Host immune response: Number of subjects with anti-drug antibodies (ADAs) [ Time Frame: Up to Week 24 ]
  • Biomarkers level related to the Epidermal growth factor receptor (EGFR) pathway [ Time Frame: Screening (Within 14 days prior to Day 1) ]
  • Quality of life assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 30 (EORTC QLQ-C30) (Version 3) [ Time Frame: Every 6 weeks up to 2.5 years ]
  • Quality of life assessed by EORTC QLQ module for colorectal cancer (EORTC QLQ-CR29) [ Time Frame: Every 6 weeks up to 2.5 years ]
  • Quality of life assessed by Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFR 18) [ Time Frame: Every 3 weeks up to 2.5 years ]
  • Number of subjects with adverse events (AEs), serious AEs, treatment emergent AEs, AEs leading to death, and AEs with National Cancer Institute-Common Terminology Criteria for AEs (NCI−CTCAE Version 4.03) Grade greater than or equal to 3 [ Time Frame: Baseline up to 28 days after the last dose administration or up to 21 months ]

Enrollment: 254
Study Start Date: March 2014
Estimated Study Completion Date: October 2017
Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Sym004
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
Sym004 is a 1:1 mixture of two mAbs which bind to two non-overlapping epitopes of the EGFR
Experimental: Arm B: Sym004
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
Sym004 is a 1:1 mixture of two mAbs which bind to two non-overlapping epitopes of the EGFR
Active Comparator: Arm C: Investigator's choice
Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.
Other: Best supportive care (BSC)
BSC will be provided at the Investigator's discretion and may include antibiotics, analgesics, antiemetics, blood transfusions and nutritional support.
Drug: 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.
Other Name: Adrucil
Drug: Capecitabine
Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.
Other Name: Xeloda

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02083653

  Show 54 Study Locations
Sponsors and Collaborators
Symphogen A/S
Investigators
Principal Investigator: Josep Tabernero, MD, PhD Vall d'Hebron University Hospital
  More Information

Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02083653     History of Changes
Other Study ID Numbers: Sym004-05
2013-003829-29 ( EudraCT Number )
EMR200637-002 ( Other Identifier: EMD Serono, Inc. / Merck KGaA )
Study First Received: March 7, 2014
Last Updated: June 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Symphogen A/S:
Metastatic Colorectal Cancer
Sym004
Best Supportive Care
Capecitabine
Fluorouracil (5-FU)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017