Squamous Cell Carcinoma of the Oral Cavity
Conditions
Keywords
Head and Neck Neoplasms, Immunotherapy, Cancer, Oral Cavity
Brief summary
The purpose of this study is to determine whether a pre-operative regimen of the study drug, IRX-2, a human cell-derived biologic with multiple active cytokine components, plus a single dose of cyclophosphamide, followed by 21 days of indomethacin, zinc-containing multivitamins, and omeprazole is active in treatment of oral cavity cancer. The regimen is intended to stimulate an immune response against the cancer.
Detailed description
This study will assess the activity and safety of the IRX Regimen in participants with newly diagnosed, untreated, surgically resectable squamous cell cancer of the oral cavity. Participants will be randomly assigned to receive either Regimen 1: IRX-2 + cyclophosphamide + indomethacin + zinc + omeprazole, or Regimen 2: cyclophosphamide + indomethacin + zinc + omeprazole. The primary study hypothesis is that the Regimen 1 with IRX-2 prolongs event-free survival and overall survival when compared to Regimen 2 without IRX-2. Subjects will be randomized to either Regimen 1 or Regimen 2 on a 2:1 basis and treated prior to surgery.
Interventions
BIOLOGICALIRX-2
Method of Administration: Administered for 10 days as subcutaneous bilateral injections in the upper neck.
DRUGCyclophosphamide
Method of Administration: Cyclophosphamide is administered once by IV
DRUGIndomethacin
Method of Administration: Indomethacin is administered orally for 21 days.
DIETARY_SUPPLEMENTZinc-containing multivitamin
Method of Administration: Zinc-containing multivitamin is administered orally for 21 days.
DRUGOmeprazole
Method of Administration: Omeprazole is administered orally for 21 days
Sponsors
Brooklyn ImmunoTherapeutics, LLC
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
1. Pathologically confirmed (histology or cytology) clinical Stage II, III, or IVA squamous cell cancer of the oral cavity (excluding lip). Subjects must be staged using AJCC Cancer Staging Manual Edition 7.0 (appendices 1 and 2). 2. Disease surgically resectable with curative intent 3. Hematological function: hemoglobin \>9 g/dL; lymphocyte count \>0.50 x 109/L; neutrophil count \>1.5 x 109/L; platelet count \>100 x 109/L 4. Hepatic function: serum albumin \>3.0 g/dL; aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \<3x the upper limits of normal (ULN); alkaline phosphatase \<2x the ULN 5. Prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.4x the ULN 6. Calculated creatinine clearance \> 50 mL/minute (Appendix 4) 7. At least 18 years of age 8. Willing and able to give informed consent and adhere to protocol therapy 9. Karnofsky performance status (KPS) \>=70% 10. Females of childbearing potential (not surgically sterile or less than 12 months post-menopausal) must be able and willing to use a highly effective form of pregnancy prevention from the time of screening, during the study and 30 days after last dose of study regimen. Males with a partner of childbearing potential must use condoms with spermicide from the date of screening to 30 days after their last dose of study regimen 11. Negative urine/serum pregnancy test, if applicable
Exclusion criteria
1. Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care of this oral cavity cancer. 2. Any medical contraindications or previous therapy that would preclude treatment with either IRX 2 Regimen 1 or 2 or the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately * Live vaccines should ideally not be administered to any patients undergoing treatment with chemotherapy or immunotherapy, but if need be, they should be administered \>4 months prior to the initiation of treatment or \>4 months after the completion of all treatment * Inactivated vaccines should precede the initiation of any study regimen and/or standard adjuvant therapy by at least 2 weeks, but preferably 4 weeks or longer 3. Clinical status of either subject or tumor such that administration of 21 day neoadjuvant IRX-2 Regimen 1 or 2 before surgery would be medically inappropriate 4. Tumor of the oropharynx 5. Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer: * involvement of pterygopalatine fossa, maxillary sinus, or facial skin;. * gross extension of tumor to the skull base; * pterygoid plate erosion; * sphenoid bone or foramen ovale involvement; * direct extension to involve prevertebral fascia; * extension to superior nasopharynx or Eustachian tube; * direct extension into the neck with involvement of the deep neck musculature (neck node fixation); * suspected invasion (encasement) of the common or internal carotid arteries. Encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270º or greater; * direct extension of neck disease to involve the external skin; * direct extension to mediastinal structures; * regional metastases to the supraclavicular neck (low level IVB or VB) 6. Any investigational agent within the previous 30 days. 7. Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days. 8. Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors, that can not, in the documented opinion of the investigator, safely be interrupted from at least 2 days prior to the initiation of the study regimen until after surgical resection of the tumor. 9. Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease. Patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded 10. Myocardial infarction within the last 3 months 11. Distant metastases (M1 disease). 12. Known infection with hepatitis B, hepatitis C, or HIV. 13. Signs or symptoms of systemic bacterial infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection). 14. Clinically significant gastritis or peptic ulcer disease that would contraindicate the use of indomethacin. 15. Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months. 16. Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid, or indomethacin. 17. Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations). 18. Prior axillary dissection. 19. Breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS)- Number of Participants With an Event | From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months) | EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization. |
| EFS- Time to Event | From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months) | EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization. Assessment of progression/disease recurrence occurred by physical exam and annual imaging for the duration of the follow up portion of the study. Median EFS was estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS)- Number of Participants With an Event | From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months) | OS was defined as the time from randomization to death due to any cause. |
| OS- Time to Event | From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months) | OS was defined as the time from randomization to death due to any cause. Data for partipants who were alive at the end of the study were censored at the last known alive date. Median OS was estimated using the Kaplan-Meier method. |
Countries
Brazil, Canada, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Regimen 1 IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamins, and omeprazole as neoadjuvant and adjuvant therapy.
IRX-2: Method of Administration: Administered for 10 days as subcutaneous bilateral injections in the upper neck.
Cyclophosphamide: Method of Administration: Cyclophosphamide is administered once by IV.
Indomethacin: Method of Administration: Indomethacin is administered orally for 21 days.
Zinc-containing multivitamins: Method of Administration: Zinc-containing multivitamins are administered orally for 21 days.
Omeprazole: Method of Administration: Omeprazole is administered orally for 21 days | 70 |
| Regimen 2 Regimen 1 but without IRX-2.
Cyclophosphamide: Method of Administration: Cyclophosphamide is administered once by IV.
Indomethacin: Method of Administration: Indomethacin is administered orally for 21 days.
Zinc-containing multivitamins: Method of Administration: Zinc-containing multivitamins are administered orally for 21 days.
Omeprazole: Method of Administration: Omeprazole is administered orally for 21 days. | 35 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 19 | 9 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 1 |
Baseline characteristics
| Characteristic | Regimen 1 | Regimen 2 | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years | 61 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 12 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 22 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Primary Disease Stage Primary disease Stage I/II | 26 Participants | 11 Participants | 37 Participants |
| Primary Disease Stage Primary disease Stage III/IV | 44 Participants | 24 Participants | 68 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 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 | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) White | 58 Participants | 25 Participants | 83 Participants |
| Region of Enrollment Brazil | 24 participants | 11 participants | 35 participants |
| Region of Enrollment Canada | 2 participants | 0 participants | 2 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 43 participants | 24 participants | 67 participants |
| Sex: Female, Male Female | 22 Participants | 10 Participants | 32 Participants |
| Sex: Female, Male Male | 48 Participants | 25 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 70 | 11 / 35 |
| other Total, other adverse events | 65 / 68 | 31 / 35 |
| serious Total, serious adverse events | 29 / 68 | 14 / 35 |
Outcome results
Primary
EFS- Time to Event
EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization. Assessment of progression/disease recurrence occurred by physical exam and annual imaging for the duration of the follow up portion of the study. Median EFS was estimated using the Kaplan-Meier method.
Time frame: From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen 1 | EFS- Time to Event | 48.3 Months |
| Regimen 2 | EFS- Time to Event | NA Months |
p-value: 0.617695% CI: [0.6, 2.1]Log Rank
Primary
Event-free Survival (EFS)- Number of Participants With an Event
EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization.
Time frame: From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regimen 1 | Event-free Survival (EFS)- Number of Participants With an Event | 31 Participants |
| Regimen 2 | Event-free Survival (EFS)- Number of Participants With an Event | 15 Participants |
Secondary
OS- Time to Event
OS was defined as the time from randomization to death due to any cause. Data for partipants who were alive at the end of the study were censored at the last known alive date. Median OS was estimated using the Kaplan-Meier method.
Time frame: From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen 1 | OS- Time to Event | NA Months |
| Regimen 2 | OS- Time to Event | NA Months |
p-value: 0.509195% CI: [0.5, 2.2]Log Rank
Secondary
Overall Survival (OS)- Number of Participants With an Event
OS was defined as the time from randomization to death due to any cause.
Time frame: From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regimen 1 | Overall Survival (OS)- Number of Participants With an Event | 19 Participants |
| Regimen 2 | Overall Survival (OS)- Number of Participants With an Event | 11 Participants |
p-value: 0.388995% CI: [0.5, 2.2]Log Rank