Recurrent Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
This phase II trial studies how well intensity-modulated radiotherapy and nivolumab work together in treating patients with head and neck squamous cell cancer that has come back. Intensity-modulation radiation therapy uses varying intensities of radiation beams to kill cancer cells and shrink tumors, thereby reducing the damage to nearby healthy tissue. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving intensity-modulated radiation therapy and nivolumab may work better at treating head and neck squamous cell cancer.
Detailed description
PRIMARY OBJECTIVE: I. To assess the 1-year progression-free survival (PFS) for patients with recurrent or second primary head and neck squamous cancer treated with intensity-modulated radiation therapy (IMRT) re-irradiation with concurrent and adjuvant nivolumab. SECONDARY OBJECTIVES: I. Evaluate the 1-year (yr) overall survival (OS) of patients treated with re-irradiation and nivolumab. II. Evaluate patient quality of life (QOL). III. Evaluate patterns of failure including local, regional and distant failure rates at 1 yr. IV. Identify and estimate the incidence rate of acute and late toxicities associated with combined re-irradiation and concurrent and adjuvant nivolumab. TERTIARY OBJECTIVE: I. To identify potential biomarkers related to clinical benefit to concurrent and adjuvant nivolumab and re-irradiation in patients with recurrent or second primary (RSP) head and neck squamous cell carcinoma (HNSCC). OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2 years from the beginning of radiation therapy.
Interventions
RADIATIONIMRT
Undergo intensity-modulated radiation therapy
BIOLOGICALNivolumab
Given IV
Sponsors
Bristol-Myers Squibb
The Cleveland Clinic
Medical College of Wisconsin
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Emory University
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 recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field * Life expectancy of greater than 6 months * Patients cannot have distant metastases and have to be candidates for curative re-irradiation * Patients with salivary gland tumors are excluded (patients with nasopharynx or sinonasal cancers can participate) * Patients with unresectable disease are eligible * Patients who undergo surgical resection will be allowed regardless of human papilloma virus (HPV) status provided they have one of the following criteria: * Positive margins on pathology * Evidence of extracapsular spread on nodal pathology * Gross residual disease on postoperative or simulation imaging * N2/3 disease * T3/4 disease * Multifocal perineural invasion and/or lymphovascular space invasion * The majority of the anticipated target volume (\> 50%) must have been previously treated to ≥ 40 Gy; prior radiation therapy (RT) must have been completed \> 6 months prior to initiation of IMRT reirradiation; if previous RT records are unavailable, investigators can estimate the dose to previously treated tissues based on completion notes or other treatment history * An Eastern Cooperative Oncology Group (ECOG) performance score 0-2 * Granulocytes \> 1500/mm³ * Platelets \> 100,000/mm³ * Bilirubin \< 1.5 mg/dl * Creatinine \< 1.5 mg/dl * No other concurrent invasive malignancies treated for the past year (localized prostate cancer or early stage skin cancer are not
Exclusion criteria
) * Patients with carotid artery involvement or encasement will be allowed provided they have no symptoms related to carotid involvement * No prior exposure to immunotherapy agents * Ability to understand and the willingness to sign a written informed consent document
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-Free Survival (PFS) | 1 year from study start | 95% confidence interval will be estimated by Kaplan-Meier method for all participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pattern of Failure | 1 year from study start | To evaluate patterns of failure as local, regional, or distant. |
| Number of Participants With Overall Survival (OS) | 1 year from study start | Will be assessed using Kaplan-Meier method. |
| Number of Participants With Incidence of Acute Adverse Events | Up to 1 year from study start | Acute toxicities will be identified and their incidence rate estimated. |
| Number of Participants With Incidence of Late Adverse Events | 2 years from study start | Late toxicities will be identified and their incidence rate estimated. |
| Quality of Life (QOL) | At baseline, end of Intensity-Modulated Radiation Therapy, and weeks 18, 30, 52, and 104, baseline and month 12 | The FACT-HN (Functional Assessment of Cancer Therapy-Head and Neck) (version 4) consists of a cancer-specific questionnaire, FACT-G (Functional Assessment of Cancer Therapy - General), in addition to 12 H&N cancer-specific items (the HN subscale).The Functional Assessment of Cancer Therapy-Head and Neck Quality of Life questionnaire may be completed by the patient using paper or electronically. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Nivolumab, IMRT) Patients receive nivolumab IV over 30 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
IMRT: Undergo intensity-modulated radiation therapy
Nivolumab: Given IV | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not eligible | 11 |
Baseline characteristics
| Characteristic | Treatment (Nivolumab, IMRT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 2 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Region of Enrollment United States | 51 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 51 |
| other Total, other adverse events | 51 / 51 |
| serious Total, serious adverse events | 24 / 51 |
Outcome results
Primary
Number of Participants With Progression-Free Survival (PFS)
95% confidence interval will be estimated by Kaplan-Meier method for all participants.
Time frame: 1 year from study start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Nivolumab, IMRT) | Number of Participants With Progression-Free Survival (PFS) | 27 Participants |
Secondary
Number of Participants With Incidence of Acute Adverse Events
Acute toxicities will be identified and their incidence rate estimated.
Time frame: Up to 1 year from study start
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | fatigue | 82.4 percentage of participants |
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | dermatitis | 58.8 percentage of participants |
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | dysphagia | 54.9 percentage of participants |
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | mucositis | 49 percentage of participants |
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | dry mouth | 47.1 percentage of participants |
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Acute Adverse Events | Lymphopenia | 11.8 percentage of participants |
Secondary
Number of Participants With Incidence of Late Adverse Events
Late toxicities will be identified and their incidence rate estimated.
Time frame: 2 years from study start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Nivolumab, IMRT) | Number of Participants With Incidence of Late Adverse Events | 3 Participants |
Secondary
Number of Participants With Overall Survival (OS)
Will be assessed using Kaplan-Meier method.
Time frame: 1 year from study start
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Nivolumab, IMRT) | Number of Participants With Overall Survival (OS) | 84.4 percentage of participants |
Secondary
Number of Participants With Pattern of Failure
To evaluate patterns of failure as local, regional, or distant.
Time frame: 1 year from study start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Nivolumab, IMRT) | Number of Participants With Pattern of Failure | 2 Participants |
Secondary
Quality of Life (QOL)
The FACT-HN (Functional Assessment of Cancer Therapy-Head and Neck) (version 4) consists of a cancer-specific questionnaire, FACT-G (Functional Assessment of Cancer Therapy - General), in addition to 12 H&N cancer-specific items (the HN subscale).The Functional Assessment of Cancer Therapy-Head and Neck Quality of Life questionnaire may be completed by the patient using paper or electronically. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL
Time frame: At baseline, end of Intensity-Modulated Radiation Therapy, and weeks 18, 30, 52, and 104, baseline and month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | Baseline | 68 score on a scale | Standard Deviation 89.2 |
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | End of IMRT | 62.5 score on a scale | Standard Deviation 90 |
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | Week 18 | 62 score on a scale | Standard Deviation 93.4 |
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | Week 30 | 74.6 score on a scale | Standard Deviation 101 |
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | Week 52 | 59 score on a scale | Standard Deviation 94.5 |
| Treatment (Nivolumab, IMRT) | Quality of Life (QOL) | Week 104 | 59 score on a scale | Standard Deviation 94.5 |