Advanced Head and Neck Squamous Cell CarcinomaPhase 2NCT03254927
A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing CDX-3379 and cetuximab in people with Advanced Head and Neck Squamous Cell Carcinoma, run by Celldex Therapeutics at 10 sites in United States.
Trial summary
This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Head and Neck Squamous Cell Carcinoma
- What is being tested?
- CDX-3379 and cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesUnited States
- Study dates
- 27 Mar 2018to 16 Dec 2020
- Phase
- Phase 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
Who may be able to join
- Histologically or cytologically confirmed head and neck squamous cell carcinoma.
- Human papilloma virus (HPV) negative tumor.
- Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
- Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment.
- Measurable disease.
- Life expectancy ≥ 12 weeks.
- If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 6 months following last treatment.
- Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue).
Who cannot join
- Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.
- Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.
- Major surgery within 4 weeks prior to first dose of study treatment.
- Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
- Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment.
- Other prior malignancy, active within 3 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast.
Show all 9Show fewer
- Active, untreated central nervous system metastases.
- Active autoimmune disease or documented history of autoimmune disease.
- Significant cardiovascular disease including CHF or poorly controlled hypertension.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Medical University of South Carolina
Charleston, South Carolina, 29425
Rush University Medical center
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45267
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale Cancer Center
New Haven, Connecticut, 06511
University of Pennsylvania Hospital, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Washington University School of Medicine
St Louis, Missouri, 63110
The University of Arizona Cancer Center
Tucson, Arizona, 85724
About this study
Official title: A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma
This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.
Read the detailed description
CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote anti-tumor effects.
Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates cell growth.
This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.
Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.
Up to 45 patients will be enrolled. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.
- Being tested
- CDX-3379 and cetuximab
- Keywords
- Erbitux, Cetuximab, Oral Cancer, Oropharyngeal cancer, Laryngeal cancer, Head and Neck Squamous Cell Carcinoma
- Medical subject headings
- Mouth Neoplasms, Oropharyngeal Neoplasms, Laryngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDX-3379 and cetuximabDrug
Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.
| Study group | Role | What they receive |
|---|---|---|
| CDX-3379 and cetuximab | Experimental | During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression. Receives: Drug: CDX-3379 and cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
Measured: The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.
Secondary outcomes (6)
Clinical Benefit Response (CBR)
The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks
Measured: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
Duration of Response (DOR)
The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented
Measured: First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
Progression-free Survival (PFS)
The time from start of study drug to time of progression or death, whichever occurs first
Measured: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
Overall Survival (OS)
The time from start of study drug to death
Measured: The time from start of study drug to death from any cause (up to approximately 2 years)
Incidence of Adverse Events [Safety and Tolerability]
Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.
Measured: Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
Tumor DNA Biomarkers.
Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.
Measured: Tumor tissue is obtained during screening window via single biopsy procedure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start27 Mar 2018
- Primary completion16 Sep 2020
- Study completion16 Dec 2020
Why it stopped: Sponsor decision based on emerging risk-benefit profile
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Head and Neck Squamous Cell CarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03254927
- Sponsor's protocol ID
- CDX3379-04
- Status last verified
- Mar 2023
- First submitted
- 17 Aug 2017
- Last updated
- 3 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Duvvuri U, George J, Kim S, Alvarado D, Neumeister VM, Chenna A, Gedrich R, Hawthorne T, LaVallee T, Grandis JR, Bauman JE. Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients. Clin Cancer Res. 2019 Oct 1;25(19):5752-5758. doi: 10.1158/1078-0432.CCR-18-3453. Epub 2019 Jul 15.
PubMed 31308059
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03254927
- Acronym / sponsor ID
- CDX3379-04
- Keywords
- Erbitux, Cetuximab, Oral Cancer, Oropharyngeal cancer, Laryngeal cancer, Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision based on emerging risk-benefit profile
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 16 Sep 2020 (actual)
- Study completion
- 16 Dec 2020 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Posted 3 Apr 2023
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 study to determine the clinical benefit (how well the drug works), safety and tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.
Detailed description
CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote anti-tumor effects.
Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates cell growth.
This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.
Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.
Up to 45 patients will be enrolled. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CDX-3379 and cetuximab | Experimental | Drug: CDX-3379 and cetuximabDuring the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically or cytologically confirmed head and neck squamous cell carcinoma.
- Human papilloma virus (HPV) negative tumor.
- Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
- Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment.
- Measurable disease.
Key exclusion criteria (9 listed)
- Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.
- Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.
- Major surgery within 4 weeks prior to first dose of study treatment.
- Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
- Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment.
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 |
|---|---|---|
| CDX-3379 and cetuximabDose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab. | Drug | CDX-3379 and cetuximab |
Primary outcome
Objective Response Rate
Time frame: The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.
The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
6 secondary outcomes
Clinical Benefit Response (CBR)
Time frame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
Duration of Response (DOR)
Time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
Progression-free Survival (PFS)
Time frame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
Overall Survival (OS)
Time frame: The time from start of study drug to death from any cause (up to approximately 2 years)
Incidence of Adverse Events [Safety and Tolerability]
Time frame: Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
Tumor DNA Biomarkers.
Time frame: Tumor tissue is obtained during screening window via single biopsy procedure.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31308059Duvvuri U, George J, Kim S, Alvarado D, Neumeister VM, Chenna A, Gedrich R, Hawthorne T, LaVallee T, Grandis JR, Bauman JE. Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients. Clin Cancer Res. 2019 Oct 1;25(19):5752-5758. doi: 10.1158/1078-0432.CCR-18-3453. Epub 2019 Jul 15.
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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.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CDX-3379 and cetuximab in people with Advanced Head and Neck Squamous Cell Carcinoma, run by Celldex Therapeutics at 10 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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 3 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 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 3 Apr 2023). 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?
Objective Response Rate (time frame: The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03254927, which also lists 1 linked publication.
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 3 Apr 2023.