Head and Neck Squamous Cell CarcinomaPhase 1NCT04624113
Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma
A Phase 1 study testing Tazemetostat and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The primary aim of the phase 1 portion of the trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat in combination with a fixed dose of pembrolizumab in patients with recurrent or metastatic (RM) head and neck cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Tazemetostat and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Apr 2021to 17 Feb 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis:
- Phase 1 specific: recurrent or metastatic head and neck cancer, inclusive of cancers that originate in the head and neck, except central nervous system (CNS) cancers.
- Phase 2 specific: recurrent or metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx.
- Disease Evaluation:
- Phase 1 specific: Measurable or evaluable disease
- Phase 2 specific: Measurable disease per RECIST. Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
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- Phase 2 specific: Progression of disease, as assessed by RECIST, that occurred on prior pembrolizumab or nivolumab (given alone or with other therapy) in the last 6 months.
- Phase 2 specific: PD-L1 positive (CPS ≥ 1 by IHC, 22C3 antibody) on archived tumor tissue. If CPS not available, tumors with PD-L1 TPS ≥ 1 are also eligible (but CPS should be performed in these cases).
- Incurable disease (defined as surgery and/or radiation is unable to offer curative potential), or ineligible for (or patient declined) local therapy.
- At least 18 years of age.
- ECOG performance status ≤ 1
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 750/mcL
- Platelets ≥ 75,000/mcL
- Hemoglobin ≥ 9 g/L
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Serum creatinine <1.5x ULN or Creatinine clearance ≥ 50 mL/min by Cockcroft-Gault
- The effects of tazemetostat on the developing human fetus are unknown. For this reason and because histone methyltransferase (HMT) agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 6 months after the last day of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for 6 months after last day of treatment.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Radiation, chemotherapy, or targeted therapy within 14 days of treatment start.
- Phase 2 specific: Prior therapy with an EZH2 inhibitor.
- Investigational therapy within 21 days of treatment start.
- A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of disease.
- Has known active CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without any evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 14 days prior to first dose of study treatment.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat, pembrolizumab, or other agents used in the study.
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- Unable to swallow oral medication.
- Receiving systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of treatment. A history of severe autoimmune disorder requiring high-dose corticosteroid treatment due to prior PD-1 inhibitor is an exclusion criterion.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of treatment.
- Prior organ or allogeneic stem cell transplant.
- Has an active autoimmune disease (i.e. rheumatoid arthritis, lupus, Sjogren's syndrome) that has required IV or subcutaneous systemic treatment in the past 6 months (excluding Rituxan). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A Phase 1-2 Trial
The primary aim of the phase 1 portion of the trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat in combination with a fixed dose of pembrolizumab in patients with recurrent or metastatic (RM) head and neck cancer.
The primary aim of the phase 2 portion of the trial is to establish the proportion of patients with pembrolizumab- or nivolumab-resistant, PD-L1 positive, RM head and neck squamous-cell carcinoma (HNSCC) who achieve an objective tumor response to tazemetostat and pembrolizumab.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Tazemetostat, Pembrolizumab
- Medical subject headings
- 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.
TazemetostatDrug
Also called Tazverik
Epizyme will supply the study agent, which will be provided free of charge to the patient.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab is commercially available
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Tazemetostat + Pembrolizumab | Experimental | * Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days).
* Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend on dose level assigned
* Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles. Receives: Drug: Tazemetostat; Drug: Pembrolizumab |
| Phase 2: Tazemetostat + Pembrolizumab | Experimental | * Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days).
* Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend of recommended phase 2 determined in Phase I portion of study.
* Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles. Receives: Drug: Tazemetostat; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose of tazemetostat in combination with a fixed dose of pembrolizumab (Phase I only)
Measured: Completion of cycle 1 for all phase I participants (estimated to be 9 months)
Objective response rate (ORR) assessed by iRECIST (Phase 2 only)
-ORR: complete or partial response achieved as best response divided by those participants who have received a response evaluation (scan)
Measured: Through completion of treatment (estimated to be 5 months)
Secondary outcomes (4)
Incidence of adverse events
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Measured: From start of treatment through 28 days post-treatment (estimated to be 6 months)
Duration of response (DOR)
-Response duration will be measured from the time measurement criteria for CR/PR or iCR/iPR (whichever is first recorded) are first met until the first date that recurrent or PD is objectively documented, taking as reference the smallest measurements recorded on study (including baseline).
Measured: Through completion of treatment (estimated to be 5 months)
Progression-free survival (PFS)
-PFS is defined as the time from date of study enrollment to disease progression or death from any cause, whichever occurs first. The patients alive, without progression, are censored at the last follow-up.
Measured: Through completion of follow-up (estimated to be 17 months)
Overall survival (OS)
-OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
Measured: Through completion of follow-up (estimated to be 17 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start14 Apr 2021
- Primary completion9 Aug 2022
- Study completion17 Feb 2024
Why it stopped: Ipsen bought out Epizyme
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Epizyme, Inc.
- Responsible party
- Sponsor
- Investigators
- Douglas Adkins, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624113
- Sponsor's protocol ID
- 202011174
- Status last verified
- Feb 2024
- First submitted
- 9 Nov 2020
- Last updated
- 21 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tazemetostat and Pembrolizumab in Patients With Pembrolizumab- or Nivolumab-Resistant, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A Phase 1-2 Trial
- ClinicalTrials.gov ID
- NCT04624113
- Acronym / sponsor ID
- 202011174
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Ipsen bought out Epizyme
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Epizyme, Inc.
- Study start
- 14 Apr 2021 (actual)
- Primary completion
- 9 Aug 2022 (actual)
- Study completion
- 17 Feb 2024 (actual)
- First posted
- 10 Nov 2020 (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.
The primary aim of the phase 1 portion of the trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat in combination with a fixed dose of pembrolizumab in patients with recurrent or metastatic (RM) head and neck cancer.
The primary aim of the phase 2 portion of the trial is to establish the proportion of patients with pembrolizumab- or nivolumab-resistant, PD-L1 positive, RM head and neck squamous-cell carcinoma (HNSCC) who achieve an objective tumor response to tazemetostat and pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I: Tazemetostat + Pembrolizumab | Experimental | Drug: Tazemetostat, Drug: Pembrolizumab* Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days). * Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend on dose level assigned * Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles. |
| Phase 2: Tazemetostat + Pembrolizumab | Experimental | Drug: Tazemetostat, Drug: Pembrolizumab* Cycle 1 over 5 weeks (35 days). Subsequent cycles over 3 weeks (21 days). * Tazemetostat tablet twice per day Days 1-35 of Cycle 1, then Days 1-21 of subsequent cycles. Dose of tazemetostat will depend of recommended phase 2 determined in Phase I portion of study. * Pembrolizumab 200mg intravenous Day 15 of Cycle 1, then Day 1 of subsequent cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis:
- Disease Evaluation:
- Phase 2 specific: Progression of disease, as assessed by RECIST, that occurred on prior pembrolizumab or nivolumab (given alone or with other therapy) in the last 6 months.
- Phase 2 specific: PD-L1 positive (CPS ≥ 1 by IHC, 22C3 antibody) on archived tumor tissue. If CPS not available, tumors with PD-L1 TPS ≥ 1 are also eligible (but CPS should be performed in these cases).
- Incurable disease (defined as surgery and/or radiation is unable to offer curative potential), or ineligible for (or patient declined) local therapy.
Key exclusion criteria (12 listed)
- Radiation, chemotherapy, or targeted therapy within 14 days of treatment start.
- Phase 2 specific: Prior therapy with an EZH2 inhibitor.
- Investigational therapy within 21 days of treatment start.
- A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of disease.
- Has known active CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without any evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 14 days 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 |
|---|---|---|
| TazemetostatAlso: TazverikEpizyme will supply the study agent, which will be provided free of charge to the patient. | Drug | Phase 2: Tazemetostat + Pembrolizumab, Phase I: Tazemetostat + Pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab is commercially available | Drug | Phase 2: Tazemetostat + Pembrolizumab, Phase I: Tazemetostat + Pembrolizumab |
Primary outcome
Recommended phase 2 dose of tazemetostat in combination with a fixed dose of pembrolizumab (Phase I only)
Time frame: Completion of cycle 1 for all phase I participants (estimated to be 9 months)
Objective response rate (ORR) assessed by iRECIST (Phase 2 only)
Time frame: Through completion of treatment (estimated to be 5 months)
-ORR: complete or partial response achieved as best response divided by those participants who have received a response evaluation (scan)
4 secondary outcomes
Incidence of adverse events
Time frame: From start of treatment through 28 days post-treatment (estimated to be 6 months)
Duration of response (DOR)
Time frame: Through completion of treatment (estimated to be 5 months)
Progression-free survival (PFS)
Time frame: Through completion of follow-up (estimated to be 17 months)
Overall survival (OS)
Time frame: Through completion of follow-up (estimated to be 17 months)
Results and safety
The study was stopped early (reason given: Ipsen bought out Epizyme). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Douglas Adkins, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tazemetostat and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site 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 20 inclusion and 12 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 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was stopped early (reason given: Ipsen bought out Epizyme). Results are not available in the source record.
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?
Recommended phase 2 dose of tazemetostat in combination with a fixed dose of pembrolizumab (Phase I only) (time frame: Completion of cycle 1 for all phase I participants (estimated to be 9 months)). The study lists 2 primary outcomes in all. 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 21 Feb 2024.