|Protocol No.||1666GCC||Principal Investigator||Zandberg, Dan
|Title||1666GCC: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Determine the Safety and Efficacy of GL-0817 (with Cyclophosphamide) for the Prevention of Recurrence in HLA-A2+ Patients with High-Risk Squamous Cell Carcinoma of the Oral Cavity
Subjects in active treatment will be vaccinated with GL-0817 with the adjuvants GM-CSF (granulocyte macrophage colony-stimulating factor, also called sargramostim or Leukine®)
and poly-ICLC (Hiltonol®) 3 times at 3-week intervals followed by 7 doses at 3-month intervals beginning at the Week 18 visit. Patients will receive IV Cyclophosphamide 1 day prior to the first 3 vaccinations.
Placebo Comparator: Placebo
Subjects in placebo arm will receive placebo to cyclophosphamide (normal saline solution) followed by Poly-ICLC/GM-CSF/placebo vaccine injections on the same schedule as the GL-0817 cohort.
|Treatment||This is a multi-center, randomized, double-blind clinical trial to assess the safety and efficacy of GL-0817 as a means to prevent disease recurrence in patients considered at high-risk following surgery and adjuvant chemoradiotherapy.
|Key Eligibility||Inclusion Criteria:
-Age greater than 18 years
-Histologic diagnosis of squamous cell carcinoma of the oral cavity
-Patients must have undergone primary gross total resection (no re-resected patients are allowed) with fulfillment of at least 1 of the following histologic criteria for high-risk disease:
Histologic involvement of 2 or more regional lymph nodes
Any lymph node with histologic extracapsular extension (ECS)
Close (less than 3mm) or positive surgical margins on microscopic evaluation with no gross residual tumor
-No evidence of locoregional disease or distant metastases at screening. Subjects must have negative scans (CT, CT-PET or MRI) for locoregional recurrence, brain or lung metastases. A negative biopsy will be mandated in patients with a positive scan. Other evaluations should be performed as clinically indicated.
-No history of distant metastases.
-Tumor tissue from surgery or biopsy must be available to determine MAGE-A3 expression for correlative studies.
-Following surgery, the patient must have received external beam radiotherapy (58-66 Gy in 2 Gy fractions, 5 days per week) with concomitant cisplatin starting within 8 weeks of surgery. The cumulative dose of cisplatin the subject received must be greater than 150 mg/m2. Protocol therapy must be initiated within a period of 4-8 weeks (28-56 days) following the end of RT.
-The patient is, in the investigator's opinion, adequately recovered from the effects of surgery and chemoradiotherapy to participate in this study.
-Blood HLA-A2 phenotype
-ECOG Performance Status less than or equal to 1
-Laboratory values obtained less than or equal to 14 days prior to randomization:
Absolute neutrophil count (ANC) greater than or equal to 1500/microliters (without intervention, e.g., G-CSF)
Platelets greater than or equal to 75,000/microliters (without intervention, e.g., transfusion)
Hemoglobin greater than or equal to 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb greater than or equal to8.0 g/dl is acceptable).
Alkaline phosphatase less than or equal to 2.5 x upper limit of normal (ULN)
AST and ALT less than or equal to 2 x ULN
Creatinine less than 2 x ULN
Bilirubin less than 1.5x ULN (except for patients with Gilbert's disease, for whom the upper acceptable limit of serum bilirubin is 3mg/dL)
-A female subject is eligible to enter the study if she is:
not pregnant or nursing; Female participants must not breastfeed during the study and for a period of 30 days following the last dose.
of non-childbearing potential (i.e., women who had a hysterectomy, are postmenopausal which is defined as 1 year without menses, have both ovaries surgically removed or have current documented tubal ligation); or
of childbearing potential (i.e., women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhea [even severe], women who are perimenopausal or have just begun to menstruate. These women must have a negative serum pregnancy test at screening, and agree to one of the following:
complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent and 6 months after the last dose of study agent; or
consistent and correct use of 1 of the following highly effective methods of birth control for one month prior to the start of the study agent and 6 months after the last dose:
combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
intrauterine device (IUD)
intrauterine hormone-releasing system ( IUS)
bilateral tubal occlusion
vasectomized partner (if vasectomized is the sole sexual partner and has received medical confirmation of surgical success)
|Applicable Disease Sites||Lip, Oral Cavity and Pharynx
|Contact||Greenebaum Cancer Center Navid Saeidi, MS||