Oropharynx Squamous Cell Carcinoma
Conditions
Brief summary
The purpose of this study is to find out if the addition of nivolumab can improve 2 year progression free survival (PFS) as compared to standard of care of fractionated radiation therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate). Fractionated means the radiation will be administered in fragments or parts across multiple days.
Detailed description
PCD details were updated as RECIST is not appropriate for tumor response assessment in this population. Tumor response will be assessed via clinical assessment and PET response (determining progression and location, if any evidence of disease).
Interventions
DRUGNivolumab
Given intravenously (IV), 240 mg every 2 weeks for 4 doses concurrent with radiation therapy (RT). Following completion of RT, 480 mg given every 4 weeks for 4 doses.
DRUGCarboplatin
Given IV once per week during radiation therapy (AUC=1).
DRUGPaclitaxel
Given IV once per week during radiation therapy (30mg/m\^2)
RADIATIONRadiation Therapy
Given 5 days/week for a total of 35 doses (70 gray total).
Sponsors
University of Michigan Rogel Cancer Center
Bristol-Myers Squibb
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
* Histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization * Clinical stage: stage III AJCC 8th edition staging (cT4 or cN3) OR "matted lymph nodes" (defined as 3 LNs abutting one another with loss of intervening fat plane that is replaced with evidence of extracapsular spread) * Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup: * History/physical examination, including documentation of weight within 2 weeks prior to registration; * FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration; Zubrod Performance Status 0-1 within 2 weeks prior to registration; * Age ≥ 18; * CBC/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; Platelets ≥ 75,000 cells/mm3; Hemoglobin ≥ 9.0 g/dL AST/ALT \<3 x ULN * Total Bilirubin \<1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3 x ULN) * Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 mL/min within 2 weeks prior to registration; * Women of childbearing potential must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and for five months after the last treatment. A woman of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone (FSH) level \> 40 mIU/mL to confirm menopause. Men receiving nivolumab who are sexually active with WOCBP must agree to use effective contraception throughout their participation in the treatment phase of the study and for seven months after the last treatment. * Due to the potential for serious adverse reactions in breastfed infants from carboplatin/paclitaxel and nivolumab, women are advised not to breast-feed during treatment with carboplatin/paclitaxel or nivolumab * The patient must provide study-specific informed consent prior to study entry.
Exclusion criteria
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); * Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if \> 3 years prior to study; * Any history of active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; * Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; * Uncontrolled diarrhea; * Uncontrolled adrenal insufficiency; * Transmural myocardial infarction within the last 3 months; * Acute bacterial or fungal infection requiring systemic antibiotics at the time of registration; * Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; * Acquired Immune Deficiency Syndrome (AIDS) with CD4+ count \< 350 cells per microL; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. * Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. * Women who are breastfeeding and are not willing to discontinue breastfeeding during the trial * Poorly controlled diabetes (defined as fasting glucose level \> 200 mg/dL) despite 2 attempts to improve glucose control by fasting duration and adjustment of medications. Patients with diabetes will preferably be scheduled in the morning and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians * Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Short bursts of steroids of 5-7 days (for COPD exacerbation or other similar indication) are allowed. * Known history of, or any evidence of active, non-infectious pneumonitis. * Known history of active TB (Bacillus Tuberculosis). * Hypersensitivity to nivolumab or any of its excipients or known hypersensitivity to carboplatin/paclitaxel. * Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Received a live vaccine within 30 days of planned start of study therapy. * Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 2 years after completion of study treatment | Estimated using the Kaplan-Meier method. Evaluated using imaging and clinical exams |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Progressed in Any Location | Up to 2 years after completion of study treatment | To characterize patterns of failure, investigators will summarize the proportion of patients who progressed in any location and whether the first progression was local, regional, distant or in multiple locations. |
| Overall Survival (OS) | 2 years after completion of study treatment | Estimated using the Kaplan-Meier method |
| Incidence of Acute Toxicity | at 1 month post chemoradiation | Toxicity evaluation per CTCAE v 5.0 |
| Incidence of Late Toxicity | 12 months post chemoradiation | Toxicity evaluation per CTCAE v 5.0 |
| Correlation of Mid-treatment FDG-PET Scans With Post-treatment PET-CT. | 12 weeks after completion of study treatment | Correlation of metabolic image uptake data on mid-treatment FDG-PET scans performed between fractions 8-12 with standard 12 week post-treatment PET-CT. The number of patients with midtreatment ≥50% decrease of MTV2.5 from baseline. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichelle Mierzwa, M.D.
University of Michigan Rogel Cancer Center
Participant flow
Pre-assignment details
2 subjects screen failed before enrollment
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 3 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 9 / 26 |
Outcome results
None listed