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Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

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ClinicalTrials.gov Identifier: NCT02568046
Recruitment Status : Terminated (Discontinued development of Sym004 in combination with FOLFIRI)
First Posted : October 5, 2015
Results First Posted : January 9, 2019
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Brief Summary:
This is a Phase 1b/2a study investigating the safety and efficacy of Sym004, an investigational medicinal product (IMP), in combination with FOLFIRI (chemotherapy) when administered every second week (Q2W).

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Sym004 Drug: FOLFIRI Phase 1 Phase 2

Detailed Description:

In the Phase 1b (Dose-Escalation) portion of the trial, patients will be sequentially enrolled to dose-escalation cohorts until establishment of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of Sym004 in combination with FOLFIRI.

The Phase 2a (Dose-Expansion) portion of the trial is expected to begin after establishing the RP2D.

Note: In January 2017, the trial was terminated during Phase 1b and enrollment was prematurely discontinued. The primary objective changed to assess the safety of the treatment combination; collection of data for secondary and exploratory objectives was omitted.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multi-Center Phase 1b/2a Trial Investigating Different Doses of Sym004 in Combination With FOLFIRI in Patients With Metastatic Colorectal Cancer Progressing After First-Line Therapy
Actual Study Start Date : March 15, 2016
Actual Primary Completion Date : May 15, 2017
Actual Study Completion Date : May 5, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sym004 12 mg/kg + FOLFIRI
Phase 1b, Dose-Escalation: Dose Level 1
Drug: Sym004
Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind specifically to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

Drug: FOLFIRI
The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).
Other Names:
  • Irinotecan (Camptosar)
  • Folinic Acid (Leucovorin)
  • Fluorouracil (5-FU)

Experimental: Sym004 9 mg/kg + FOLFIRI
Phase 1b, Dose-Escalation: Dose Level -1
Drug: Sym004
Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind specifically to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

Drug: FOLFIRI
The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).
Other Names:
  • Irinotecan (Camptosar)
  • Folinic Acid (Leucovorin)
  • Fluorouracil (5-FU)

Experimental: Sym004 (RP2D) + FOLFIRI
Phase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI
Drug: Sym004
Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind specifically to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

Drug: FOLFIRI
The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).
Other Names:
  • Irinotecan (Camptosar)
  • Folinic Acid (Leucovorin)
  • Fluorouracil (5-FU)




Primary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). [ Time Frame: 15 months ]
    AEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. The incidence and type of AEs (e.g., treatment-emergent AE [TEAE]) were summarized according to MedDRA system organ classes and preferred terms. An AE was considered as treatment-emergent if it occurred after the first treatment administration.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main inclusion Criteria:

  1. Male or female, at least 18 years of age at the time of informed consent
  2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  3. Histologically or cytologically confirmed, locally advanced or metastatic colorectal cancer (CRC) that is documented to be without Kirsten rat sarcoma (KRAS) or neuroblastoma rat sarcoma (NRAS) gene mutations (i.e., tumors must express the KRAS and NRAS wild type [WT], exon 2, 3 and 4).
  4. Failed (defined as radiologic progression) treatment for locally advanced or metastatic disease with first-line combination therapy of oxaliplatin and a fluoropyrimidine, with or without bevacizumab, during treatment or < 3 months after the last dose of first-line therapy and within < 3 months of C1/D1. Patients who discontinued first-line therapy due to toxicity may be enrolled provided progression occurred < 6 months after the last dose of the first-line therapy regimen.

    or Failed (defined as radiologic progression) adjuvant therapy with combination therapy of oxaliplatin and a fluoropyrimidine during treatment or within < 6 months after the last dose of oxaliplatin and within < 6 months of C1/D1.

  5. Eligible for FOLFIRI
  6. Measurable disease according to RECIST v1.1

Main exclusion Criteria:

  1. Prior therapy with anti-EGFR antibodies, anti-EGFR small molecule inhibitors or irinotecan (CPT-11)
  2. Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1
  3. Significant gastrointestinal abnormalities
  4. Patients with a significant cardiovascular disease or condition
  5. Abnormal hematologic, renal or hepatic function

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02568046


Locations
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United States, California
UCLA School of Medicine
Los Angeles, California, United States, 90095
Sharp Memorial Hosptal
San Diego, California, United States, 92123
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Georgia
University Cancer & Blood Center, LLC
Athens, Georgia, United States, 30607
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Spain
Hospital del Mar
Barcelona, Spain, 08003
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Madrid Sanchinarro
Madrid, Spain, 28050
Sponsors and Collaborators
Symphogen A/S
Investigators
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Principal Investigator: Josep Tabernero, MD, PhD Vall d'Hebron University Hospital
  Study Documents (Full-Text)

Documents provided by Symphogen A/S:
Study Protocol  [PDF] February 22, 2017
Statistical Analysis Plan  [PDF] June 7, 2017


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Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02568046     History of Changes
Other Study ID Numbers: Sym004-09
2015-003047-19 ( EudraCT Number )
First Posted: October 5, 2015    Key Record Dates
Results First Posted: January 9, 2019
Last Update Posted: March 26, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Symphogen A/S:
Metastatic Colorectal Cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances