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Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

Primary Purpose

Metastatic Colorectal Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Sym004
FOLFIRI
Sponsored by
Symphogen A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA School of Medicine
  • Sharp Memorial Hosptal
  • Georgetown University Medical Center
  • University Cancer & Blood Center, LLC
  • University of Michigan Health System
  • Hospital del Mar
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario Madrid Sanchinarro

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Sym004 12 mg/kg + FOLFIRI

Sym004 9 mg/kg + FOLFIRI

Sym004 (RP2D) + FOLFIRI

Arm Description

Phase 1b, Dose-Escalation: Dose Level 1

Phase 1b, Dose-Escalation: Dose Level -1

Phase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

Full Information

First Posted
September 30, 2015
Last Updated
March 14, 2019
Sponsor
Symphogen A/S
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1. Study Identification

Unique Protocol Identification Number
NCT02568046
Brief Title
Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
Discontinued development of Sym004 in combination with FOLFIRI
Study Start Date
March 15, 2016 (Actual)
Primary Completion Date
May 15, 2017 (Actual)
Study Completion Date
May 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Symphogen A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sym004 12 mg/kg + FOLFIRI
Arm Type
Experimental
Arm Description
Phase 1b, Dose-Escalation: Dose Level 1
Arm Title
Sym004 9 mg/kg + FOLFIRI
Arm Type
Experimental
Arm Description
Phase 1b, Dose-Escalation: Dose Level -1
Arm Title
Sym004 (RP2D) + FOLFIRI
Arm Type
Experimental
Arm Description
Phase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI
Intervention Type
Drug
Intervention Name(s)
Sym004
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Other Intervention Name(s)
Irinotecan (Camptosar), Folinic Acid (Leucovorin), Fluorouracil (5-FU)
Intervention Description
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).
Primary Outcome Measure Information:
Title
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).
Description
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.
Time Frame
15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main inclusion Criteria: Male or female, at least 18 years of age at the time of informed consent Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 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). 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. Eligible for FOLFIRI Measurable disease according to RECIST v1.1 Main exclusion Criteria: Prior therapy with anti-EGFR antibodies, anti-EGFR small molecule inhibitors or irinotecan (CPT-11) Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1 Significant gastrointestinal abnormalities Patients with a significant cardiovascular disease or condition Abnormal hematologic, renal or hepatic function
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josep Tabernero, MD, PhD
Organizational Affiliation
Vall d'Hebron University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Sharp Memorial Hosptal
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University Cancer & Blood Center, LLC
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Madrid Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

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