Colon Cancer, Breast Cancer, Cancer of the Head and NeckPhase 1SYN004_Ph_1NCT02391727
Safety, Immunogenicity and Pharmacokinetics of SYN004 in Patients With Solid Tumors
A Phase 1 study testing SYN004 in people with Colon Cancer, Breast Cancer, Cancer of the Head and Neck, run by Synermore Biologics Co., Ltd. at 2 sites in United States.
Trial summary
A first-in-human evaluation of SYN004, a monoclonal antibody that binds to the EGF receptor on cancer cells. Cetuximab, a marketed antibody, has been shown to be effective by inhibiting the growth of cancer cells thereby prolonging the life of patients who have received it. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colon Cancer, Breast Cancer, Cancer of the Head and Neck
- What is being tested?
- SYN004
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2015to Oct 2018
- Phase
- Phase 1
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Note: No waivers of the study inclusion or exclusion criteria will be granted.
- Diagnosis of a solid tumor for which the accepted standard of care includesa licensed anti-EGFR therapy;
- Tumor progression in patients with RAS wild type metastatic colorectal cancer irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies; OR Tumor progression in patients with metastatic colorectal cancer refractory to cetuximab or panitumumab or other anti-EGFR antibodies OR Tumor progression in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have refused therapy.
- OR Tumor progression or recurrence in patients with squamous cell carcinoma of the head and neck irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies.
- OR Patients with locally advanced or metastatic colorectal carcinoma who have
- relapsed after standard of care treatment,
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- proved refractory to standard of care treatment
- refused standard of care treatment
- been found to be medically unsuitable for standard of care treatment
- Completion of written informed consent procedure;
- Male or female subjects over 17 years of age
- Life expectancy of at least 3 months;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2;
- At least one measureable non-irradiated site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- Adequate bone marrow function, with absolute neutrophil count (ANC) >1,500/mm3, platelet count >100,000/mm3, and hemoglobin > 10 g/mm3;
- Adequate liver function, with bilirubin <1.5 x the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x the ULN;
- Adequate renal function, with serum creatinine <1.5 mg/dL;
- Adequate cardiac function, with left ventricular ejection fraction (LVEF) ≥50%, normal electrocardiogram, and absence of significant cardiac disease;
- In women of childbearing potential (defined as women of reproductive capacity who are pre-menopausal or within 12 months of cessation of menses): negative serum pregnancy test and use of an acceptable non-hormonal method of contraception;
- Ability to communicate with the investigator, and understand and comply with the requirements of the protocol;
- Agrees to notify the investigator when deviating from the protocol requirements with regard to concomitant medications;
- Agrees to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study.
Who cannot join
- Participation in a study of an investigational agent or use of an investigational device at the time of screening or within 4 weeks of enrollment;
- Receipt of treatment with a monoclonal antibody (mAb) within 4 weeks of enrollment or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to treatment with a mAb administered >4 weeks before enrollment;
- Receipt of chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment, or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to a previously-administered agent;
- Major surgical procedure or significant traumatic injury within 4 weeks prior to screening;
- Diagnosis of an additional malignancy that is progressing and requires treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy;
- Active autoimmune disease requiring systemic treatment within the past 3 months, or a documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents (subjects with vitiligo or resolved childhood asthma/atopy are allowed);
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- Diagnosis of an immune deficiency;
- Receipt of systemic steroids or any form of immunosuppressive therapy within 7 days prior to enrollment, with the following exceptions:
- Stable doses of topical, ocular, intranasal or inhaled corticosteroids
- Doses of systemic steroids that, in the opinion of the investigator, are pysiologic replacement doses
- Systemic steroids as prophylactic treatment for subjects with allergy to contrast media
- Non-absorbed intra-articular steroid injections
- Systemic corticosteroids required for control of infusion reactions or AEs if doses have been tapered to <10 mg prednisone or equivalent for 2 weeks prior to the first study treatment
- Evidence of interstitial lung disease or active, non-infectious pneumonitis;
- Active infection requiring systemic therapy;
- History of cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within 6 months prior to screening;
- Active hepatitis B (i.e., hepatitis B surface antigen [HBsAg] positive) or hepatitis C (i.e., hepatitis C virus [HCV] ribonucleic acid [RNA; qualitative] is detected);
- Serious non-healing wound, ulcer, or bone fracture;
- Any severe or uncontrolled medical condition or other condition that could affect participation in the study;
- Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ochsner Medical Center
New Orleans, Louisiana, 70121
Washington University Medical Center
St Louis, Missouri, 63110
About this study
Official title: A Phase 1, Multi-center, Open-Label Dose Escalation Study of SYN004 in Patients With Solid Tumors to Evaluate the Safety, Immunogenicity and Pharmacokinetics of SYN004 Following Administration of Eight Intravenous Doses
A first-in-human evaluation of SYN004, a monoclonal antibody that binds to the EGF receptor on cancer cells. Cetuximab, a marketed antibody, has been shown to be effective by inhibiting the growth of cancer cells thereby prolonging the life of patients who have received it. SYN004 is a closely related monoclonal antibody also binds to the EGF receptor in the same way. SYN004 might also inhibit cancer cells and prolong life but has been engineered to avoid some of the hypersensitivity reactions known to provoked by cetuximab.
Read the detailed description
Study Design:
In this open-label, dose escalation study, subjects will receive a single IV loading dose of SYN004 on Day 1 of the first treatment week, followed by up to 7 fixed weekly doses of SYN004. Subjects will be assigned to loading and fixed doses by dose group.
Each dose group will comprise 3 subjects and may be expanded to 6 subjects. Subjects will enter dose groups in the order in which they are enrolled. There will be no intra-subject dose adjustments.
Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day; at least 1 day must elapse before the next subject in the cohort receives the loading dose.
Study SYN004-001 Dose Matrix. Three initial subjects will be enrolled followed by an additional three if specified by protocol. Dose levels are specified below.
Group 1: Loading dose: 100 mg/m2; Weekly Dose: 62.5 mg/m2. Group 2: Loading dose: 200 mg/m2; Weekly Dose: 125 mg/m2. Group 3: Loading dose: 400 mg/m2; Weekly Dose: 250 mg/m2.
After each dose of IV SYN004, subjects will be observed in the clinic for 12 hours. After the loading dose, subjects will undergo safety evaluations on Days 2, 3 and 5. Safety evaluation will also be performed on Day 1 (pre-treatment) and Day 3 of each fixed dose treatment week.
Dose-limiting toxicities (DLTs) are defined as any Grade ≥3 AE assessed by the investigator or Medical Monitor, with agreement of the Safety Review Board (SRB), as related to SYN004. Subjects with DLTs will be withdrawn from treatment. If 2 or more subjects in a dose group experience DLTs, or one subject in a dose group experiences a Grade ≥3 infusion reaction, all subjects in that dose group will be withdrawn from treatment.
Subjects in the dose groups are considered evaluable for dose escalation decisions if they receive at least 4 doses of SYN004, or discontinue SYN004 because of a DLT.
Subjects who withdraw or are terminated per protocol before receiving 4 doses of SYN004 will be replaced.
For subjects who receive at least 4 doses of SYN004, End of Study CT scans for RECIST (version 1.1) evaluation will be performed six (6) days following the final SYN004 treatment.
There will be a 28-day safety monitoring period following the final dose of SYN004 for all subjects in the study. All subjects will attend an End-of-Study Visit 28 days after the final dose of SYN004.
Subjects who complete Cycles 1 and 2, who have evidence of improvement per RECIST 1.1 (i.e., findings of complete or partial response per RECIST 1.1) and meet the other eligibility criteria will be offered up to 3 additional treatment cycles (i.e., up to 12 additional weekly doses) of SYN004 in the SYN004-001 Extension Study. During the Extension Study, subjects will receive the same fixed dose of SYN004 they received in Cycles 1 and 2.
Dose escalation will proceed according to a standard 3+3 study design.
- Being tested
- SYN004
- Keywords
- SYN004, cetuximab
- Medical subject headings
- Colonic Neoplasms, Breast Neoplasms, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYN004Biological
subjects who have received effective treatment for their cancers are eligible
| Study group | Role | What they receive |
|---|---|---|
| SYN004 | Other | open label study Receives: Biological: SYN004 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events
cutaneous toxicity, hypersensitivity
Measured: 28 days of last SYN004 Administration
Secondary outcomes (9)
maximum plasma concentration (Cmax)
Cmax will be determined using noncompartmental methods for SYN004
Measured: 84 days
time to Cmax (Tmax)
Tmax will be determined using noncompartmental methods for SYN004
Measured: 84 days
elimination rate constant (λz)
λz will be determined using noncompartmental methods for SYN004
Measured: 84 days
elimination half-life (t½)
t½ will be determined using noncompartmental methods for SYN004
Measured: 84 days
mean residence time (MRT)
MRT will be determined using noncompartmental methods for SYN004
Measured: 84 days
area under the plasma concentration vs. time curve from 0 (initiation of infusion) to the time of the last detectable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-∞)
AUC0-t and AUC0-∞ will be determined using noncompartmental methods for SYN004
Measured: 84 days
systemic clearance (CL)
CL will be determined using noncompartmental methods for SYN004
Measured: 84 days
volume of distribution in the terminal phase (Vdβ), and estimated steady-state volume of distribution (VSS)
Vdβ and VSS will be determined using noncompartmental methods for SYN004
Measured: 84 days
anti-cancer activity
Measurement of objective response (OR), durability of objective response (DOR), and progression-free survival (PFS). The number and proportion of subjects who achieve objective tumor response (complete response [CR], partial response [PR], and CR+PR) or stable disease (SD) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, according to local radiological assessments from date of first administration of the investigational product to the end of the study treatment.
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon Cancer, Breast Cancer, Cancer of the Head and NeckStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Synermore Biologics Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John McClain, MD, Study director, Synermore Biologics Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02391727
- Sponsor's protocol ID
- SYN004-001
- Acronym
- SYN004_Ph_1
- Status last verified
- Nov 2018
- First submitted
- 9 Mar 2015
- Last updated
- 16 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multi-center, Open-Label Dose Escalation Study of SYN004 in Patients With Solid Tumors to Evaluate the Safety, Immunogenicity and Pharmacokinetics of SYN004 Following Administration of Eight Intravenous Doses
- ClinicalTrials.gov ID
- NCT02391727
- Acronym / sponsor ID
- SYN004_Ph_1 / SYN004-001
- Keywords
- SYN004, cetuximab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Synermore Biologics Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- May 2015 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 18 Mar 2015 (estimated)
- 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.
A first-in-human evaluation of SYN004, a monoclonal antibody that binds to the EGF receptor on cancer cells. Cetuximab, a marketed antibody, has been shown to be effective by inhibiting the growth of cancer cells thereby prolonging the life of patients who have received it. SYN004 is a closely related monoclonal antibody also binds to the EGF receptor in the same way. SYN004 might also inhibit cancer cells and prolong life but has been engineered to avoid some of the hypersensitivity reactions known to provoked by cetuximab.
Detailed description
Study Design:
In this open-label, dose escalation study, subjects will receive a single IV loading dose of SYN004 on Day 1 of the first treatment week, followed by up to 7 fixed weekly doses of SYN004. Subjects will be assigned to loading and fixed doses by dose group.
Each dose group will comprise 3 subjects and may be expanded to 6 subjects. Subjects will enter dose groups in the order in which they are enrolled. There will be no intra-subject dose adjustments.
Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day; at least 1 day must elapse before the next subject in the cohort receives the loading dose.
Study SYN004-001 Dose Matrix. Three initial subjects will be enrolled followed by an additional three if specified by protocol. Dose levels are specified below.
Group 1: Loading dose: 100 mg/m2; Weekly Dose: 62.5 mg/m2. Group 2: Loading dose: 200 mg/m2; Weekly Dose: 125 mg/m2. Group 3: Loading dose: 400 mg/m2; Weekly Dose: 250 mg/m2.
After each dose of IV SYN004, subjects will be observed in the clinic for 12 hours. After the loading dose, subjects will undergo safety evaluations on Days 2, 3 and 5. Safety evaluation will also be performed on Day 1 (pre-treatment) and Day 3 of each fixed dose treatment week.
Dose-limiting toxicities (DLTs) are defined as any Grade ≥3 AE assessed by the investigator or Medical Monitor, with agreement of the Safety Review Board (SRB), as related to SYN004. Subjects with DLTs will be withdrawn from treatment. If 2 or more subjects in a dose group experience DLTs, or one subject in a dose group experiences a Grade ≥3 infusion reaction, all subjects in that dose group will be withdrawn from treatment.
Subjects in the dose groups are considered evaluable for dose escalation decisions if they receive at least 4 doses of SYN004, or discontinue SYN004 because of a DLT.
Subjects who withdraw or are terminated per protocol before receiving 4 doses of SYN004 will be replaced.
For subjects who receive at least 4 doses of SYN004, End of Study CT scans for RECIST (version 1.1) evaluation will be performed six (6) days following the final SYN004 treatment.
There will be a 28-day safety monitoring period following the final dose of SYN004 for all subjects in the study. All subjects will attend an End-of-Study Visit 28 days after the final dose of SYN004.
Subjects who complete Cycles 1 and 2, who have evidence of improvement per RECIST 1.1 (i.e., findings of complete or partial response per RECIST 1.1) and meet the other eligibility criteria will be offered up to 3 additional treatment cycles (i.e., up to 12 additional weekly doses) of SYN004 in the SYN004-001 Extension Study. During the Extension Study, subjects will receive the same fixed dose of SYN004 they received in Cycles 1 and 2.
Dose escalation will proceed according to a standard 3+3 study design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SYN004 | Other | Biological: SYN004open label study |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Note: No waivers of the study inclusion or exclusion criteria will be granted.
- Diagnosis of a solid tumor for which the accepted standard of care includesa licensed anti-EGFR therapy;
- Tumor progression in patients with RAS wild type metastatic colorectal cancer irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies; OR Tumor progression in patients with metastatic colorectal cancer refractory to cetuximab or panitumumab or other anti-EGFR antibodies OR Tumor progression in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have refused therapy.
- OR Tumor progression or recurrence in patients with squamous cell carcinoma of the head and neck irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies.
- OR Patients with locally advanced or metastatic colorectal carcinoma who have
Key exclusion criteria (20 listed)
- Participation in a study of an investigational agent or use of an investigational device at the time of screening or within 4 weeks of enrollment;
- Receipt of treatment with a monoclonal antibody (mAb) within 4 weeks of enrollment or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to treatment with a mAb administered >4 weeks before enrollment;
- Receipt of chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment, or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to a previously-administered agent;
- Major surgical procedure or significant traumatic injury within 4 weeks prior to screening;
- Diagnosis of an additional malignancy that is progressing and requires treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy;
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 |
|---|---|---|
| SYN004subjects who have received effective treatment for their cancers are eligible | Biological | SYN004 |
Primary outcome
Number of patients with adverse events
Time frame: 28 days of last SYN004 Administration
cutaneous toxicity, hypersensitivity
9 secondary outcomes
maximum plasma concentration (Cmax)
Time frame: 84 days
time to Cmax (Tmax)
Time frame: 84 days
elimination rate constant (λz)
Time frame: 84 days
elimination half-life (t½)
Time frame: 84 days
mean residence time (MRT)
Time frame: 84 days
area under the plasma concentration vs. time curve from 0 (initiation of infusion) to the time of the last detectable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-∞)
Time frame: 84 days
systemic clearance (CL)
Time frame: 84 days
volume of distribution in the terminal phase (Vdβ), and estimated steady-state volume of distribution (VSS)
Time frame: 84 days
anti-cancer activity
Time frame: 84 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Individual participant dataSharing planned: No
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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.
John McClain, MD study director
Synermore Biologics Co., Ltd.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SYN004 in people with Colon Cancer, Breast Cancer, Cancer of the Head and Neck, run by Synermore Biologics Co., Ltd. at 2 sites in United States.
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 22 inclusion and 20 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: finished, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 patients with adverse events (time frame: 28 days of last SYN004 Administration). 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 16 Nov 2018.