Metastatic Colorectal CancerPhase 3NCT03717038
Sym004 Versus TAS-102 in Patients With mCRC
A Phase 3 study testing Sym004 and TAS-102 in people with Metastatic Colorectal Cancer and Colorectal Cancer Metastatic, run by Symphogen A/S.
Trial summary
This is a Phase 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, Colorectal Cancer Metastatic, Carcinoma
- What is being tested?
- Sym004 and TAS-102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2019to Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
Who may be able to join
- Male or female patients, ≥ 18 years of age (≥ 20 years of age in Japan) at the time of obtaining informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS of 70% to 100%).
- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic.
- Meeting the protocol definition of DNmCRC as assessed in the screening blood test.
- mCRC not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
- Measurable or non-measurable disease according to the Response Evaluation Criteria in Solid Tumors (Version 1.1) (RECIST v1.1).
- Must have received ≥ 2 prior regimens of standard therapy for mCRC, or 1 prior regimen of standard adjuvant therapy and ≥ 1 prior regimen of standard therapy for mCRC, with failure of those regimens (due to refractory, relapsed, or progressive disease [PD], or due to intolerance warranting discontinuation and precluding retreatment with the same agent prior to PD). If one of the regimens utilized for inclusion is adjuvant therapy, the patient must have experienced documented recurrence by imaging studies within ≤ 6 months of completion of that therapy. Prior standard chemotherapy must have included agents as specified in the protocol (where approved in the country).
- Persons of childbearing potential agreeing to use a highly effective method of contraception during the study, beginning within 2 weeks prior to the first dose of protocol therapy and continuing until 3 months after the last dose of Sym004 or 6 months after the last dose of TAS-102; male patients must also agree to refrain from sperm donation during these periods.
Who cannot join
- Women who are pregnant or intending to become pregnant before, during, or within 3 months after the last dose of Sym004 or 6 months after the last dose of TAS-102; women who are breastfeeding.
- Prior history of specific mutations (specified in the protocol) in the tumor tissue at the time of any previous assessment.
- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- An active second malignancy or history of another malignancy within 5 years prior to randomization, with exceptions.
- Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to randomization, unless adequately treated and considered by the Investigator to be stable.
- Active uncontrolled bleeding or a known bleeding diathesis.
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- Known clinically significant cardiovascular disease or condition.
- Non-healing wounds on any part of the body.
- Significant gastrointestinal abnormality.
- Skin rash of Grade > 1 from prior anti-EGFR or other therapy at the time of randomization.
- Any other unresolved Grade > 1 toxicity associated with prior antineoplastic therapy, with exceptions.
- Known or suspected hypersensitivity to any of the excipients of formulated Sym004 or TAS-102.
- Drugs and Other Treatments Exclusion Criteria:
- Prior treatment with either TAS-102 or regorafenib.
- Antineoplastic agents for the primary malignancy (standard or investigational) within 3 weeks prior to randomization and during study; includes chemotherapy, immunotherapy, or other biological therapy.
- Other investigational treatments within 3 weeks prior to randomization and during study; includes participation in medical device or other therapeutic intervention clinical trial.
- Radiotherapy within 3 weeks prior to randomization.
- Immunosuppressive or glucocorticoid therapy (> 10 mg daily prednisone or equivalent), within 2 weeks prior to randomization and during study; includes systemic or enteric corticosteroids.
- Prophylactic use of hematopoietic growth factors within 1 week prior to randomization and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated.
About this study
Official title: A Phase 3, Randomized, Open-Label, Multicenter Trial of Sym004 Versus Trifluridine/Tipiracil (TAS-102) in Patients With Chemotherapy-Refractory or Relapsed Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR Monoclonal Antibody Therapy
This is a Phase 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent.
Read the detailed description
Randomization is in the ratio of 1:1 to either Sym004 (Arm A) or TAS-102 (Arm B) in genomically-selected patients with chemotherapy-refractory or relapsed metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy.
Following consent, centralized genomic analysis will be conducted on blood samples obtained from each potential patient. Double-negative (DN) results as defined in trial inclusion criteria will be required for initial eligibility prior to randomization. Patients with DNmCRC will continue in the screening process. Once deemed fully eligible, patients will be randomized to either Arm A or Arm B (collectively referred to as protocol therapy).
Dosing cycles of 28 days with the assigned protocol therapy will continue until a protocol-specified discontinuation criterion is met. Following treatment discontinuation, patients will continue to be followed for OS.
- Being tested
- Sym004, TAS-102
- Keywords
- Metastatic Colorectal Cancer, Colorectal Cancer Metastatic, Carcinoma, Sym004, futuximab, modotuximab, TAS-102, Trifluridine, Tipiracil, Lonsurf
- Medical subject headings
- Colorectal Neoplasms, Carcinoma
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 two recombinant mAbs (futuximab and modotuximab) which bind specifically to non-overlapping epitopes located in the extracellular domain (ECD) of the EGFR.
TAS-102Drug
Also called Trifluridine/Tipiracil, Lonsurf
TAS-102 is a combination of trifluridine, a thymidine-based nucleic acid analogue, and tipiracil, a thymidine phosphorylase inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Sym004) | Experimental | Sym004 will be administered as a loading dose of 9 mg/kg on Cycle 1 Day 1, followed by weekly doses of 6 mg/kg beginning Cycle 1 Day 8. Receives: Drug: Sym004 |
| Arm B (TAS-102) | Active comparator | TAS-102 is commercially available and will be administered as per local prescribing instructions. Receives: Drug: TAS-102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS) time following treatment with Sym004 versus TAS-102.
Time (in months) from the date of randomization to the date of death. In the absence of death confirmation or for patients alive as of the OS data cut-off date (i.e., date upon reaching 445 deaths), OS will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier.
Measured: Assessed up to 5 years.
Secondary outcomes (8)
Antineoplastic Efficacy: Progression Free Survival (PFS) as assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time (in months) from the date of randomization until the date of the investigator-assessed radiological disease progression or death due to any cause.
Investigator-assessed radiological disease progression (per RECIST v1.1) with the following key censoring rules:
- Patients who are alive with no disease progression as of the analysis cut-off date will be censored at the date of the last tumor assessment.
- Patients who receive non-study cancer treatment before disease progression will be censored at the date of the last evaluable tumor assessment before the initiation of non-study cancer treatment.
- Patients with clinical, but not radiologic, evidence of progression will be censored at the date of the last evaluable tumor assessment before the clinical progression assessment.
Measured: Assessed up to 5 years.
Antineoplastic Efficacy: Objective Response Rate (ORR) as assessed by RECIST v1.1.
Defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). Assessed approximately every 8 weeks (at the end of even-numbered cycles).
Measured: Assessed up to 5 years.
Antineoplastic Efficacy: Disease Control Rate (DCR) as assessed by RECIST v1.1.
Defined as the proportion of patients with objective evidence of CR, PR, or stable disease (SD). Assessed approximately every 8 weeks (at the end of even-numbered cycles).
Measured: Assessed up to 5 years.
Antineoplastic Efficacy: Duration of Response (DOR) as assessed by RECIST v1.1.
Time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, with the same censoring rules as for PFS.
Measured: Assessed up to 5 years.
Sym004 Safety Evaluation: Occurrence and nature of adverse events (AEs) on a weekly dosing regimen.
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology and the severity of the toxicities will be graded according to the Common Terminology Criteria for Adverse Events (Version 5) (CTCAE v5), where applicable, from signing of informed consent up to 30 days after the final dose of Sym004.
Measured: Assessed up to 5 years.
Immunogenicity Assessment: Number of subjects with anti-drug antibodies (ADAs) to Sym004 over time.
Serum sampling to assess the potential for ADA formation are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Day 1 of odd numbered cycles thereafter, the End of Treatment Visit, and the 1-Month Follow-up Visit.
Measured: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Trough Concentration (Cmin)
Cmin is defined as the serum concentration at the start of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.
Measured: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Maximum Concentration (Cmax)
Cmax is defined as the serum concentration at the end of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.
Measured: Assessed up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study startFeb 2019 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2025 (estimated)
Why it stopped: Study was withdrawn due to administrative reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 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 Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03717038
- Sponsor's protocol ID
- Sym004-12
- Other IDs
- 2018-003187-31, 2018
- Status last verified
- Jan 2019
- First submitted
- 18 Oct 2018
- Last updated
- 4 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- 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 4 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Open-Label, Multicenter Trial of Sym004 Versus Trifluridine/Tipiracil (TAS-102) in Patients With Chemotherapy-Refractory or Relapsed Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR Monoclonal Antibody Therapy
- ClinicalTrials.gov ID
- NCT03717038
- Acronym / sponsor ID
- Sym004-12
- Keywords
- Metastatic Colorectal Cancer, Colorectal Cancer Metastatic, Carcinoma, Sym004, futuximab, modotuximab, TAS-102, Trifluridine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was withdrawn due to administrative reasons
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- Feb 2019 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 23 Oct 2018 (actual)
- Results
- Not posted in the source record
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 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent.
Detailed description
Randomization is in the ratio of 1:1 to either Sym004 (Arm A) or TAS-102 (Arm B) in genomically-selected patients with chemotherapy-refractory or relapsed metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy.
Following consent, centralized genomic analysis will be conducted on blood samples obtained from each potential patient. Double-negative (DN) results as defined in trial inclusion criteria will be required for initial eligibility prior to randomization. Patients with DNmCRC will continue in the screening process. Once deemed fully eligible, patients will be randomized to either Arm A or Arm B (collectively referred to as protocol therapy).
Dosing cycles of 28 days with the assigned protocol therapy will continue until a protocol-specified discontinuation criterion is met. Following treatment discontinuation, patients will continue to be followed for OS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (Sym004) | Experimental | Drug: Sym004Sym004 will be administered as a loading dose of 9 mg/kg on Cycle 1 Day 1, followed by weekly doses of 6 mg/kg beginning Cycle 1 Day 8. |
| Arm B (TAS-102) | Active comparator | Drug: TAS-102TAS-102 is commercially available and will be administered as per local prescribing instructions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients, ≥ 18 years of age (≥ 20 years of age in Japan) at the time of obtaining informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS of 70% to 100%).
- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic.
- Meeting the protocol definition of DNmCRC as assessed in the screening blood test.
- mCRC not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
Key exclusion criteria (19 listed)
- Women who are pregnant or intending to become pregnant before, during, or within 3 months after the last dose of Sym004 or 6 months after the last dose of TAS-102; women who are breastfeeding.
- Prior history of specific mutations (specified in the protocol) in the tumor tissue at the time of any previous assessment.
- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- An active second malignancy or history of another malignancy within 5 years prior to randomization, with exceptions.
- Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to randomization, unless adequately treated and considered by the Investigator to be stable.
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 two recombinant mAbs (futuximab and modotuximab) which bind specifically to non-overlapping epitopes located in the extracellular domain (ECD) of the EGFR. | Drug | Arm A (Sym004) |
| TAS-102Also: Trifluridine/Tipiracil, LonsurfTAS-102 is a combination of trifluridine, a thymidine-based nucleic acid analogue, and tipiracil, a thymidine phosphorylase inhibitor. | Drug | Arm B (TAS-102) |
Primary outcome
Overall survival (OS) time following treatment with Sym004 versus TAS-102.
Time frame: Assessed up to 5 years.
Time (in months) from the date of randomization to the date of death. In the absence of death confirmation or for patients alive as of the OS data cut-off date (i.e., date upon reaching 445 deaths), OS will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier.
8 secondary outcomes
Antineoplastic Efficacy: Progression Free Survival (PFS) as assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Objective Response Rate (ORR) as assessed by RECIST v1.1.
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Disease Control Rate (DCR) as assessed by RECIST v1.1.
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Duration of Response (DOR) as assessed by RECIST v1.1.
Time frame: Assessed up to 5 years.
Sym004 Safety Evaluation: Occurrence and nature of adverse events (AEs) on a weekly dosing regimen.
Time frame: Assessed up to 5 years.
Immunogenicity Assessment: Number of subjects with anti-drug antibodies (ADAs) to Sym004 over time.
Time frame: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Trough Concentration (Cmin)
Time frame: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Maximum Concentration (Cmax)
Time frame: Assessed up to 5 years.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2019.
- Individual participant dataSharing planned: Undecided
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CRC
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 Institute of Oncology
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sym004 and TAS-102 in people with Metastatic Colorectal Cancer and Colorectal Cancer Metastatic, run by Symphogen A/S.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Overall survival (OS) time following treatment with Sym004 versus TAS-102. (time frame: Assessed up to 5 years.). 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 4 Feb 2019.