Recurrent Head and Neck Squamous Cell CarcinomaPhase 1/2NCT04220775
Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer
A Phase 1/2 study testing Bintrafusp Alfa, Quality-of-Life Assessment and Questionnaire Administration in people with Recurrent Head and Neck Squamous Cell Carcinoma and Second Primary Squamous Cell Carcinoma of the Head and Neck, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the side effects and how well bintrafusp alfa and stereotactic body radiation therapy work in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has occurred after having cancer in the past (second primary). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Bintrafusp Alfa, Quality-of-Life Assessment and Questionnaire Administration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Mar 2020to 3 Oct 2022
- 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
Who may be able to join
- Patients with histologically documented local-regional recurrent squamous cell carcinoma of the head and neck, or second primary squamous cell carcinoma of the head and neck
- Patients must be willing to undergo research biopsy for tissue collection at baseline and at disease progression
- Previous receipt of at least 30 Gy of radiation for head and neck squamous cell cancer (HNSCC) with overlapping fields
- Not eligible or poor candidate or patient refusal of surgery for recurrence
- Evaluable disease apparent on imaging (MRI or computed tomography [CT])
- 1 to 3 sites of recurrence (< 60 cm^3 per site, total volume < 100 cm^3)
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- Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2
- White blood count (WBC) >= 2000/L
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Platelets >= 100,000 cells/mm^3
- Hemoglobin >= 9.0 g/dl; Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 9.0 g/dl is acceptable
- Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (except patients with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal
- Negative serum pregnancy test for women of childbearing potential and confirmation within 24 hours of first dose of study drug
Who cannot join
- Presence of distant metastases
- Less than six-month disease free interval from end of prior radiotherapy to the head and neck
- Prior receipt of anti-PD-1/L1
- Patients who are pregnant or breast feeding
- Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device; myocardial infarction within 3 months of registration
- Active autoimmune disorder or immunosuppression (including human immunodeficiency virus [HIV], but excluding endocrine abnormalities that are controlled with replacement medications)
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- Active viral hepatitis
- Steroid therapy of greater than prednisone 10 mgs a day or equivalent
- Prior history of invasive non-head and neck cancer within two years, with the exception of screen detected prostate cancer treated with observation only, basal cell and squamous cell carcinoma of the skin, and micro-invasive resected cervical carcinoma
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study of M7824 Plus Curative Intent Re-Irradiation With Stereotactic Body Radiation Therapy (SBRT) in Patients With Local-Regionally Recurrent Head and Neck Squamous Cell Carcinoma
This phase I/II trial studies the side effects and how well bintrafusp alfa and stereotactic body radiation therapy work in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has occurred after having cancer in the past (second primary). Immunotherapy with bintrafusp alfa may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving bintrafusp alfa and stereotactic body radiation therapy may help to control recurrent head and neck squamous cell cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety, tolerability and feasibility of bintrafusp alfa (M7824) when administered together with stereotactic body radiation therapy (SBRT) reirradiation. (Lead In) II. To evaluate the progression-free survival (PFS) rate of M7824 plus SBRT reirradiation at 1 year. (Phase 2)
SECONDARY OBJECTIVES:
- To evaluate the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST).
II. To evaluate the 1-year locoregional control (LRC), locoregional failure-free survival (LFFS), distant metastasis (DM) and overall survival (OS) rates.
III. To evaluate acute and late toxicity using Common Terminology Criteria for Adverse Events (CTCAE) - version (v) 5.0.
IV. To evaluate fibrosis-related toxicities and functional outcomes. V. To evaluate patient reported outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI).
VI. To evaluate volumetric tumor regression rate and magnetic resonance imaging (MRI) kinetic biomarkers after M7824 plus SBRT.
VII. To compare quality-adjusted-life-years (QALY) between M7824 plus SBRT reirradiation and historic SBRT reirradiation control.
EXPLORATORY OBJECTIVE:
- Biomarkers will be accessed in the tumor and blood samples and correlated with clinical outcomes and toxicity.
OUTLINE:
Patients receive bintrafusp alfa intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once every other day (QOD) for 2 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 6 months for 3 years.
- Conditions
- Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
- Being tested
- Bintrafusp Alfa, Quality-of-Life Assessment, Questionnaire Administration, Stereotactic Body Radiation Therapy
- 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.
Bintrafusp AlfaDrug
Also called Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Stereotactic Body Radiation TherapyRadiation
Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Undergo SBRT
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bintrafusp alfa, SBRT) | Experimental | Patients receive bintrafusp alfa IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once QOD for 2 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bintrafusp Alfa; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
For the phase I part of this phase I/II study, the primary endpoint was DLT defined as any grade 3 or above AE resulting in inability to complete radiotherapy due to toxicity related to M7824 or the combination of M7824 and SBRT.
Measured: The DLT window is from first M7824 dose (D0) until 14 days post SBRT (D28).
Secondary outcomes (8)
Progression-free Survival (PFS) Rate at 1 Year
For the phase II part of this phase I/II study, the primary endpoint was to evaluate progression-free survival (PFS) at 1 year. Progression-free survival was defined as from treatment start to progression, or death, whichever occurred first, or to the last follow-up.
Measured: Up to 1 year
Overall Response by RECIST
Best overall response by RECIST 1.1
Measured: Tumor reassessment during treatment
Overall Survival (OS)
OS was defined was from treatment start to death or to the last follow-up
Measured: Up to 1 year
To Evaluate Acute and Late Toxicity Using Common Terminology Criteria for Adverse Events (CTCAE)-v5.0
Common Terminology Criteria for Adverse Events (CTCAE)-v5.0
Measured: Up to 1 year
To Evaluate Fibrosis-related Toxicities and Functional Outcomes
Measured: up to 1 year
To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI)
Measured: up to 1 year
To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT
Measured: up to 1 year
To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start18 Mar 2020
- Primary completion3 Oct 2022
- Study completion3 Oct 2022
Why it stopped: The sponsor decided to no longer develop the drug and stop support of studies using the drug.
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 Recurrent Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Renata Ferrarotto, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04220775
- Sponsor's protocol ID
- 2019-0608
- Other IDs
- NCI-2019-07625, 2019-0608
- Status last verified
- Jul 2024
- First submitted
- 26 Nov 2019
- Last updated
- 7 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.
PubMed 33720067
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of M7824 Plus Curative Intent Re-Irradiation With Stereotactic Body Radiation Therapy (SBRT) in Patients With Local-Regionally Recurrent Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04220775
- Acronym / sponsor ID
- 2019-0608
- Conditions
- Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to no longer develop the drug and stop support of studies using the drug.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 18 Mar 2020 (actual)
- Primary completion
- 3 Oct 2022 (actual)
- Study completion
- 3 Oct 2022 (actual)
- First posted
- 7 Jan 2020 (actual)
- Results
- Posted 23 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects and how well bintrafusp alfa and stereotactic body radiation therapy work in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has occurred after having cancer in the past (second primary). Immunotherapy with bintrafusp alfa may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving bintrafusp alfa and stereotactic body radiation therapy may help to control recurrent head and neck squamous cell cancer.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety, tolerability and feasibility of bintrafusp alfa (M7824) when administered together with stereotactic body radiation therapy (SBRT) reirradiation. (Lead In) II. To evaluate the progression-free survival (PFS) rate of M7824 plus SBRT reirradiation at 1 year. (Phase 2)
SECONDARY OBJECTIVES:
- To evaluate the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST).
II. To evaluate the 1-year locoregional control (LRC), locoregional failure-free survival (LFFS), distant metastasis (DM) and overall survival (OS) rates.
III. To evaluate acute and late toxicity using Common Terminology Criteria for Adverse Events (CTCAE) - version (v) 5.0.
IV. To evaluate fibrosis-related toxicities and functional outcomes. V. To evaluate patient reported outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI).
VI. To evaluate volumetric tumor regression rate and magnetic resonance imaging (MRI) kinetic biomarkers after M7824 plus SBRT.
VII. To compare quality-adjusted-life-years (QALY) between M7824 plus SBRT reirradiation and historic SBRT reirradiation control.
EXPLORATORY OBJECTIVE:
- Biomarkers will be accessed in the tumor and blood samples and correlated with clinical outcomes and toxicity.
OUTLINE:
Patients receive bintrafusp alfa intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once every other day (QOD) for 2 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 6 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bintrafusp alfa, SBRT) | Experimental | Drug: Bintrafusp Alfa, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Radiation: Stereotactic Body Radiation TherapyPatients receive bintrafusp alfa IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once QOD for 2 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with histologically documented local-regional recurrent squamous cell carcinoma of the head and neck, or second primary squamous cell carcinoma of the head and neck
- Patients must be willing to undergo research biopsy for tissue collection at baseline and at disease progression
- Previous receipt of at least 30 Gy of radiation for head and neck squamous cell cancer (HNSCC) with overlapping fields
- Not eligible or poor candidate or patient refusal of surgery for recurrence
- Evaluable disease apparent on imaging (MRI or computed tomography [CT])
Key exclusion criteria (9 listed)
- Presence of distant metastases
- Less than six-month disease free interval from end of prior radiotherapy to the head and neck
- Prior receipt of anti-PD-1/L1
- Patients who are pregnant or breast feeding
- Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device; myocardial infarction within 3 months of registration
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 |
|---|---|---|
| Bintrafusp AlfaAlso: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CGiven IV | Drug | Treatment (bintrafusp alfa, SBRT) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (bintrafusp alfa, SBRT) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (bintrafusp alfa, SBRT) |
| Stereotactic Body Radiation TherapyAlso: SABR, SBRT, Stereotactic Ablative Body Radiation TherapyUndergo SBRT | Radiation | Treatment (bintrafusp alfa, SBRT) |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: The DLT window is from first M7824 dose (D0) until 14 days post SBRT (D28).
For the phase I part of this phase I/II study, the primary endpoint was DLT defined as any grade 3 or above AE resulting in inability to complete radiotherapy due to toxicity related to M7824 or the combination of M7824 and SBRT.
8 secondary outcomes
Progression-free Survival (PFS) Rate at 1 Year
Time frame: Up to 1 year
Overall Response by RECIST
Time frame: Tumor reassessment during treatment
Overall Survival (OS)
Time frame: Up to 1 year
To Evaluate Acute and Late Toxicity Using Common Terminology Criteria for Adverse Events (CTCAE)-v5.0
Time frame: Up to 1 year
To Evaluate Fibrosis-related Toxicities and Functional Outcomes
Time frame: up to 1 year
To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI)
Time frame: up to 1 year
To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT
Time frame: up to 1 year
To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control
Time frame: up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33720067Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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.
Renata Ferrarotto principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bintrafusp Alfa, Quality-of-Life Assessment and Questionnaire Administration in people with Recurrent Head and Neck Squamous Cell Carcinoma and Second Primary Squamous Cell Carcinoma of the Head and Neck, run by M.D. Anderson Cancer Center 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 15 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 7 Nov 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 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 23 Jul 2024). 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?
Dose Limiting Toxicity (DLT) (time frame: The DLT window is from first M7824 dose (D0) until 14 days post SBRT (D28).). 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 NCT04220775, 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 7 Nov 2024.