Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer
Brief summary
This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for Squamous Cell Carcinoma of the oral cavity. The following drugs are involved in this study: * Nivolumab (Opdivo™) * Ipilimumab (Yervoy™)
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The purpose of this study is to evaluate effectiveness (how well the drug/s work) of Nivolumab or Nivolumab combined with Ipilimumab prior to standard of care surgery. Nivolumab and Ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. Both nivolumab and Ipilimumab have been demonstrated to activate the immune system to attack cancer cells in laboratory studies and in patients with different types of cancers. Nivolumab (Opdivo ™) has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin cancer), and specific types of previously treated advanced lung and kidney cancers. Ipilimumab (Yervoy™) is approved by the FDA for the treatment of metastatic melanoma. Because Nivolumab and Ipilimumab help the immune system work in different ways, the combination of Nivolumab and Ipilimumab was tested in laboratory studies. The data from these studies suggested that giving the two drugs together could be of benefit to patients, and this was indeed found to be the case in patients with melanoma. The combination of Nivolumab and Ipilimumab is now FDA approved as treatment for patients with metastatic melanoma. However, the use of Nivolumab as well as Ipilimumab alone or in combination for the treatment of patients with head and neck cancer is not approved. Results from clinical trials investigating the safety and efficacy of Nivolumab and Ipilimumab in patients with head and neck cancer are not available at this time. In the proposed study, either Nivolumab or the combination of Nivolumab and Ipilimumab is being tested is being tested prior to surgery to remove cancers of the oral cavity. By stimulating the immune system to attack cancer cells, these drugs may cause the cancer to decrease in size prior to surgery and prevent the cancer from coming back.
Interventions
Sponsors
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed squamous cell carcinoma of the oral cavity. Clinical stage \>=T2 (primary tumor greater than 2 cm in size) and/or evidence of regional nodal involvement by clinical exam or imaging * Only patients 18 years and older are eligible. There is no upper age limit but the patients must be able to medically tolerate the regimen. Adverse event data are currently unavailable on the use immune checkpoint blockade for participants \< 18 years of age, and thus children are excluded from this study * ECOG performance status \<=1 * Patients much be a surgical candidate (e.g. their disease must be considered resectable before any treatment and must have no serious medical contraindications that definitively preclude undergoing general anesthesia) Ability to understand and the willingness to sign a written informed consent document * Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception (see Appendix B). WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. WOCBP is defined as any woman or adolescent who has begun menstruation and is not post- menopausal. A post-menopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months * Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab * Men who are sexually active with WOCBP must agree to use any contraceptive method (see Appendix B) with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception) * Participants must have normal organ and marrow function as defined below: Laboratory parameters: WBC ≥ 2000/uL, Absolute neutrophil count (ANC) ≥ 1500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin (Hgb) ≥ 9 g/dL; Hgb-A1C ≤ 7.5%; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); Bilirubin ≤ 2.5 × ULN (≤ 4 × ULN for subjects with Gilbert's disease); Alkaline phosphatase ≤ 2.5 × ULN; Creatinine ≤ 1.5 × ULN
Exclusion criteria
* Pathologically proven, radiologic or clinical evidence of distant metastatic disease (this includes all disease below the clavicles, as well as disease metastatic to the bone, brain, or in the spinal canal) * Any prior immunologic cancer therapy with systemic inhibitors of the PD-1 or CTLA-4 pathway * Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Individuals with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; or if diagnosed and treated within the past 2 years for cervical cancer in situ or basal cell or squamous cell carcinoma of the skin * Prior radiation to the head and neck region * Prior chemotherapy within the last 2 years * History of pneumonitis or interstitial lung disease * Has evidence of active, noninfectious pneumonitis that required treatment with steroids. * Active, suspected or prior documented autoimmune disease that has required systemic treatment in the last 2 years with immune modifying agents (e.g. replacement therapy such as thyroxine, insulin or physiologic corticosteroids is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Volumetric Response Rate to Treatment | At time of surgery | Response rate to window treatment with single agent nivolumab or nivolumab combined with ipilimumab is determined using bidirectional measurements (product of longest 2 diameters of lesions) of primary and nodal lesions to be removed at the time of surgery. Responders will have demonstrated any reduction in overall tumor volume as determined by the product of the longest perpendicular bidirectional tumor measurements. |
| Safety and Tolerability of Protocol Treatment | At the time of surgery | Outcome measure includes number of participants with treatment-related adverse events as assessed by CTCAE v4.0, number of dose-limiting toxicities in safety run-ins following a 3 + 3 design, and delays to surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Demonstrating Objective Response Using RECIST Criteria | At time of surgery | Determining the radiologic response rate following the window treatment as determined by RECIST v1.1. |
| Percentage of Participants Demonstrating Pathological Response | At time of surgery | Pathologic response in the primary tumor was assessed using a quantitative grading scheme: pathologic tumor response \[nonviable tumor\] PTR0 = no or \<10% response PTR1 = ≥10% PTR2 = ≥50% |
| Participant One Year Progression-Free Survival Percentage | 1 year | Progression-free survival is defined as the time between first study treatment and either recurrent disease or death. Recurrent disease includes a local failure, regional failure, or distant metastasis. |
| Participant Overall Survival Percentage | Data Cutoff (14.2 Months Median Follow Up) | Overall survival is defined as the time between first study treatment and death. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJonathan Schoenfeld, MD
Dana-Farber Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab With Ipilimumab * Nivolumab to be delivered at a pre-determine dose for two weeks
* Ipilimumab to be delivered at a pre-determine dose for one week
* Blood Sample Collected
* Standard of Care Surgery
Nivolumab
Ipilimumab
Standard of Care Surgery | 15 |
| Nivolumab * Nivolumab to be delivered at a pre-determine dose for two weeks
* Blood Sample Collected
* Standard of Care Surgery
Nivolumab
Standard of Care Surgery | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Nivolumab With Ipilimumab | Nivolumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 15 | 2 / 15 |
| other Total, other adverse events | 12 / 15 | 11 / 15 |
| serious Total, serious adverse events | 2 / 15 | 3 / 15 |
Outcome results
Primary
Percentage of Participants With a Volumetric Response Rate to Treatment
Response rate to window treatment with single agent nivolumab or nivolumab combined with ipilimumab is determined using bidirectional measurements (product of longest 2 diameters of lesions) of primary and nodal lesions to be removed at the time of surgery. Responders will have demonstrated any reduction in overall tumor volume as determined by the product of the longest perpendicular bidirectional tumor measurements.
Time frame: At time of surgery
Population: Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab With Ipilimumab | Percentage of Participants With a Volumetric Response Rate to Treatment | 53 percentage of participants |
| Nivolumab | Percentage of Participants With a Volumetric Response Rate to Treatment | 50 percentage of participants |
Primary
Safety and Tolerability of Protocol Treatment
Outcome measure includes number of participants with treatment-related adverse events as assessed by CTCAE v4.0, number of dose-limiting toxicities in safety run-ins following a 3 + 3 design, and delays to surgery.
Time frame: At the time of surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab With Ipilimumab | Safety and Tolerability of Protocol Treatment | Delays to Surgery | 0 instances |
| Nivolumab With Ipilimumab | Safety and Tolerability of Protocol Treatment | Dose-Limiting Toxic Effects during Safety Run-In | 0 instances |
| Nivolumab With Ipilimumab | Safety and Tolerability of Protocol Treatment | Grade 3-4 Events At Least Possibly Related to Protocol Treatment | 5 instances |
| Nivolumab | Safety and Tolerability of Protocol Treatment | Delays to Surgery | 0 instances |
| Nivolumab | Safety and Tolerability of Protocol Treatment | Dose-Limiting Toxic Effects during Safety Run-In | 0 instances |
| Nivolumab | Safety and Tolerability of Protocol Treatment | Grade 3-4 Events At Least Possibly Related to Protocol Treatment | 2 instances |
Secondary
Participant One Year Progression-Free Survival Percentage
Progression-free survival is defined as the time between first study treatment and either recurrent disease or death. Recurrent disease includes a local failure, regional failure, or distant metastasis.
Time frame: 1 year
Population: Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab With Ipilimumab | Participant One Year Progression-Free Survival Percentage | 85 percentage of participants |
Secondary
Participant Overall Survival Percentage
Overall survival is defined as the time between first study treatment and death.
Time frame: Data Cutoff (14.2 Months Median Follow Up)
Population: Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab With Ipilimumab | Participant Overall Survival Percentage | 89 percentage of participants |
Secondary
Percentage of Participants Demonstrating Objective Response Using RECIST Criteria
Determining the radiologic response rate following the window treatment as determined by RECIST v1.1.
Time frame: At time of surgery
Population: For this analysis, patients with no radiographically measurable lesions on imaging review were excluded. Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab With Ipilimumab | Percentage of Participants Demonstrating Objective Response Using RECIST Criteria | 38 percentage of participants |
| Nivolumab | Percentage of Participants Demonstrating Objective Response Using RECIST Criteria | 13 percentage of participants |
Secondary
Percentage of Participants Demonstrating Pathological Response
Pathologic response in the primary tumor was assessed using a quantitative grading scheme: pathologic tumor response \[nonviable tumor\] PTR0 = no or \<10% response PTR1 = ≥10% PTR2 = ≥50%
Time frame: At time of surgery
Population: Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab With Ipilimumab | Percentage of Participants Demonstrating Pathological Response | PTR1 | 40 percentage of participants |
| Nivolumab With Ipilimumab | Percentage of Participants Demonstrating Pathological Response | PTR2 | 33 percentage of participants |
| Nivolumab | Percentage of Participants Demonstrating Pathological Response | PTR1 | 38 percentage of participants |
| Nivolumab | Percentage of Participants Demonstrating Pathological Response | PTR2 | 15 percentage of participants |