Status and phase
Conditions
Treatments
About
This is a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment must be diagnosed with non-metastatic, biopsy-proven stage II-IVB oral cavity, stage III-IVB larynx and hypopharynx, or stage III-IVB HPV/p16 negative intermediate-high risk oropharynx head and neck cancer, and must be eligible and amenable to surgical resection.
Full description
This study will be enrolled using a 3+3 model. Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients will proceed to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Histologically or cytologically confirmed: stage II-IVB oral cavity, stage III-IVB larynx, stage III-IVB hypopharynx, or stage III-IVB HPV and/or p16 negative intermediate-high risk oropharynx head and neck cancer (AJCC 8th edition)
Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm by CT, PET/CT or MRI or >10 mm on visual inspection by clinical exam
Patients who are deemed resectable by ENT surgeon without pre-existing medical conditions that could inhibit surgery following neoadjuvant therapy, and do not refuse surgery
Written informed consent and HIPAA authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
Age > 18 years at time of study entry
ECOG performance status ≤ 1
Life expectancy ≥ 24 weeks
Body weight >30kg
Adequate normal organ and marrow function as defined below:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85
72 x serum creatinine (mg/dL)
Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
Exclusion criteria
Participation in another clinical study with an investigational product during the last 3 months
Patients with active ILD / pneumonitis or with a history of ILD/ pneumonitis requiring steroids
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug for patients who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C. (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
Patients with QTc interval > 470 msec during screening
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion:
Any concurrent chemotherapy, IP, biologic, or hormonal therapy that is not part of standard NCCN indicated HNSCC adjuvant concurrent CRT. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
History of allogenic organ or bone marrow transplantation
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of another primary malignancy except for:
History of leptomeningeal carcinomatosis
History of active primary immunodeficiency
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Prior randomisation or treatment in a previous durvalumab clinical study
Patients with p16-positive oropharyngeal SCCA. No verification of p16 status is needed for laryngeal cancer or oral cavity cancer.
Patients with sinonasal SCCAs
Patients with metastatic SCCA neck disease with an unknown primary tumor site
Patients with distant metastatic disease on initial screening imaging
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements
Primary purpose
Allocation
Interventional model
Masking
21 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal