Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief 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). 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: I. 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: I. 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: I. 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.
Interventions
DRUGBintrafusp Alfa
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
RADIATIONStereotactic Body Radiation Therapy
Undergo SBRT
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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) * 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
Exclusion criteria
* 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) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response by RECIST | Tumor reassessment during treatment | Best overall response by RECIST 1.1 |
| Overall Survival (OS) | Up to 1 year | OS was defined was from treatment start to death or to the last follow-up |
| To Evaluate Acute and Late Toxicity Using Common Terminology Criteria for Adverse Events (CTCAE)-v5.0 | Up to 1 year | Common Terminology Criteria for Adverse Events (CTCAE)-v5.0 |
| Progression-free Survival (PFS) Rate at 1 Year | Up to 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. |
| To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI) | up to 1 year | — |
| To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT | up to 1 year | — |
| To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control | up to 1 year | — |
| To Evaluate Fibrosis-related Toxicities and Functional Outcomes | up to 1 year | — |
Countries
United States
Participant flow
Recruitment details
3 participants were registered, 1 participants were not treated, not eligible or inevaluable, Participant withdrew before screening completed.
Pre-assignment details
The study was planned to enroll 8 patients in phase 1 to assess safety and toxicity. However, based on sponsored analytical findings of other trials using this drug the sponsor decided to no longer develop the drug and stop support of studies using the drug. The study was ended early. Three participants were registered, 2 of them were treated and 1 of them withdrew before screening completed.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Bintrafusp Alfa + SBRT Participants 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. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Disease Progression | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1 Bintrafusp Alfa + SBRT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 60.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Primary
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.
Time frame: The DLT window is from first M7824 dose (D0) until 14 days post SBRT (D28).
Population: The two participants who were enrolled in phase 1 part of the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Bintrafusp Alfa + SBRT | Dose Limiting Toxicity (DLT) | DLT | 0 Participants |
| Phase 1 Bintrafusp Alfa + SBRT | Dose Limiting Toxicity (DLT) | No DLT | 2 Participants |
| Phase 2 Bintrafusp Alfa + SBRT | Dose Limiting Toxicity (DLT) | DLT | 0 Participants |
| Phase 2 Bintrafusp Alfa + SBRT | Dose Limiting Toxicity (DLT) | No DLT | 0 Participants |
Secondary
Overall Response by RECIST
Best overall response by RECIST 1.1
Time frame: Tumor reassessment during treatment
Population: The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase II part of this study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Bintrafusp Alfa + SBRT | Overall Response by RECIST | Partial response | 1 Participants |
| Phase 1 Bintrafusp Alfa + SBRT | Overall Response by RECIST | Progressive disease | 1 Participants |
| Phase 2 Bintrafusp Alfa + SBRT | Overall Response by RECIST | Partial response | 0 Participants |
| Phase 2 Bintrafusp Alfa + SBRT | Overall Response by RECIST | Progressive disease | 0 Participants |
Secondary
Overall Survival (OS)
OS was defined was from treatment start to death or to the last follow-up
Time frame: Up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.
Secondary
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.
Time frame: Up to 1 year
Population: The study was terminated after enrollment of 2 participants in phase 1 and no participants participated in the phase II part of this study.
Secondary
To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control
Time frame: up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.
Secondary
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
Time frame: Up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.
Secondary
To Evaluate Fibrosis-related Toxicities and Functional Outcomes
Time frame: up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.
Secondary
To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI)
Time frame: up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.
Secondary
To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT
Time frame: up to 1 year
Population: This was a secondary outcome in phase 2 only. The study was terminated after enrollment of 2 patients in phase 1 and no patient participated in the phase 2 part of this study. This outcome was not analyzed because no patient was recruited in phase 2.