Metastatic Colorectal CancerPhase 1/2NCT02568046
Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients
A Phase 1/2 study testing Sym004 and FOLFIRI in people with Metastatic Colorectal Cancer, run by Symphogen A/S at 8 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Sym004 and FOLFIRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 15 Mar 2016to 5 May 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
University Cancer & Blood Center, LLC
Athens, Georgia, 30607
UCLA School of Medicine
Los Angeles, California, 90095
Sharp Memorial Hosptal
San Diego, California, 92123
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Spain3 sites
Hospital del Mar
Barcelona, 08003
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
About this study
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
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).
Read the 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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Sym004, FOLFIRI
- Keywords
- Metastatic Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sym004Drug
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).
FOLFIRIDrug
Also called Irinotecan (Camptosar), Folinic Acid (Leucovorin), Fluorouracil (5-FU)
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).
| Study group | Role | What they receive |
|---|---|---|
| Sym004 12 mg/kg + FOLFIRI | Experimental | Phase 1b, Dose-Escalation: Dose Level 1 Receives: Drug: Sym004; Drug: FOLFIRI |
| Sym004 9 mg/kg + FOLFIRI | Experimental | Phase 1b, Dose-Escalation: Dose Level -1 Receives: Drug: Sym004; Drug: FOLFIRI |
| Sym004 (RP2D) + FOLFIRI | Experimental | Phase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI Receives: Drug: Sym004; Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2015 (estimated)
- Study start15 Mar 2016
- Primary completion15 May 2017
- Study completion5 May 2018
Why it stopped: Discontinued development of Sym004 in combination with FOLFIRI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Symphogen A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Josep Tabernero, MD, PhD, Principal investigator, Vall d'Hebron University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02568046
- Sponsor's protocol ID
- Sym004-09
- Other IDs
- 2015-003047-19, 2015
- Status last verified
- Mar 2019
- First submitted
- 30 Sep 2015
- Last updated
- 26 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02568046
- Acronym / sponsor ID
- Sym004-09
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Metastatic Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Discontinued development of Sym004 in combination with FOLFIRI
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2016 (actual)
- Primary completion
- 15 May 2017 (actual)
- Study completion
- 5 May 2018 (actual)
- First posted
- 5 Oct 2015 (estimated)
- Results
- Posted 9 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sym004 12 mg/kg + FOLFIRI | Experimental | Drug: Sym004, Drug: FOLFIRIPhase 1b, Dose-Escalation: Dose Level 1 |
| Sym004 9 mg/kg + FOLFIRI | Experimental | Drug: Sym004, Drug: FOLFIRIPhase 1b, Dose-Escalation: Dose Level -1 |
| Sym004 (RP2D) + FOLFIRI | Experimental | Drug: Sym004, Drug: FOLFIRIPhase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sym004Sym004 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 | Sym004 (RP2D) + FOLFIRI, Sym004 12 mg/kg + FOLFIRI, Sym004 9 mg/kg + FOLFIRI |
| FOLFIRIAlso: Irinotecan (Camptosar), Folinic Acid (Leucovorin), Fluorouracil (5-FU)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). | Drug | Sym004 (RP2D) + FOLFIRI, Sym004 12 mg/kg + FOLFIRI, Sym004 9 mg/kg + FOLFIRI |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josep Tabernero, MD, PhD principal investigator
Vall d'Hebron University Hospital
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sym004 and FOLFIRI in people with Metastatic Colorectal Cancer, run by Symphogen A/S at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019.