Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatments sym004, best supportive care (bsc), fluorouracil (5-fu), capecitabine
Phase phase 2
Targets EGFR, KRAS
Sponsor Symphogen A/S
Start date March 2014
End date December 2016
Trial size 254 participants
Trial identifier NCT02083653, 2013-003829-29, EMR200637-002, Sym004-05

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
sym004
Sym004 will be administered as an intravenous infusion at a dose of 12 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.
(Experimental)
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.
(Active Comparator)
Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.
best supportive care (bsc)
BSC will be provided at the Investigator's discretion and may include antibiotics, analgesics, antiemetics, blood transfusions and nutritional support.
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.
capecitabine
Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Primary Outcomes

Measure
Overall survival (OS) Time
time frame: Up to 2.5 years

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Josep Tabernero, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Symphogen A/S.