Clinical trial NCT02568046: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
Lead sponsor: Symphogen A/S
Sponsor class: INDUSTRY
First posted: 2015-10-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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).
timeFrame: 15 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hosptal
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
Study officials:
affiliation: Vall d'Hebron University Hospital
name: Josep Tabernero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: