Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

NCT02568046 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: Sym004-092015-003047-19
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 8

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).

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (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).

  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.

  15 months

Study Arms (3)

Sym004 12 mg/kg + FOLFIRI

EXPERIMENTAL

Phase 1b, Dose-Escalation: Dose Level 1

Drug: Sym004; Drug: FOLFIRI

Sym004 9 mg/kg + FOLFIRI

EXPERIMENTAL

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

Drug: Sym004; Drug: FOLFIRI

Sym004 (RP2D) + FOLFIRI

EXPERIMENTAL

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

Drug: Sym004; Drug: FOLFIRI

Interventions

Sym004 DRUG

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).

Sym004 (RP2D) + FOLFIRI; Sym004 12 mg/kg + FOLFIRI; Sym004 9 mg/kg + FOLFIRI

FOLFIRI DRUG

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).

Also known as: Irinotecan (Camptosar), Folinic Acid (Leucovorin), Fluorouracil (5-FU)

Sym004 (RP2D) + FOLFIRI; Sym004 12 mg/kg + FOLFIRI; Sym004 9 mg/kg + FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (8)

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

Sharp Memorial Hosptal

San Diego, California, 92123, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

futuximab; IFL protocol; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The trial was terminated as development of Sym004 in combination with FOLFIRI was discontinued. The primary objective changed to assess the safety of the treatment combination; collection of data for secondary and exploratory objectives was omitted.

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Symphogen A/S

info@symphogen.com

+45 8838 2600

Study Officials

• Josep Tabernero, MD, PhD

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 5, 2015
• Study Start: March 15, 2016
• Primary Completion: May 15, 2017
• Study Completion: May 5, 2018
• Last Updated: March 26, 2019
• Results First Posted: January 9, 2019

Record last verified: 2019-03

Locations

ES (3); US (5)