Nivolumab Based Immunotherapy for Treatment of High Grade Cervical Dysplasia
Nivolumab Based Immunotherapy for Treatment of High Grade Cervical Dysplasia
The study design is a phase II interventional trial for women with biopsy proven high-grade
 cervical dysplasia. The study is an open label study and randomized. The study will have two
 arms. Patients will be randomized to both arms.
High-grade cervical dysplasia (cervical intraepithelial neoplasia (CIN) II/III), is both
 detectable and quantifiable, which presents many opportunities for evaluation or early
 treatment, intervention and eventually, for cancer prevention. High-grade dysplasia is
 typically detected during cervical cancer screening with a pap smear. To determine the
 pathologic response rate of high grade cervical dysplasia with PD-1 checkpoint modulation
 with Nivolumab.This is a randomized phase II trial with two experimental arms (1 dose of
 nivolumab and 3 doses of nivolumab).
Inclusion Criteria:

 -  Adult female subjects (age 18 years or older)

 -  Performance status ECOG 0-1

 -  All patients must have cervical biopsies demonstrating high-grade cervical dysplasia.

 -  All patients must have a satisfactory colposcopy with visualization of the entire
 squamo-columnar junction

 -  All patients must be candidates for a cervical conization procedure or LEEP procedure

 -  The patient is able and willing to comply with study procedures, and signed and dated
 informed consent is obtained before any study-related procedure is performed

 -  Negative screening test results for hepatitis B, hepatitis C, and human
 immunodeficiency virus

 -  At least six weeks must have elapsed from any prior chemotherapy, radiation therapy or
 immunotherapy

 -  Patients must have adequate:

 -  Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to
 1,500/mcl. Platelets greater than or equal to100, 000/mcl. Hemoglobin > 9 gm/dL.

 -  Renal function: creatinine less than or equal to institutional upper limit normal
 (ULN) or calculated creatinine clearance (Cockcroft-Gault) ≥ 50 ml/min.

 -  Serum creatinine </= 1.5xULN or creatinine clearance (CrCl) >/=50 mL/min (using
 the Cockcroft-Gault formula)

 -  Female CrCl = (140-age in years) x weight in kg x 0.85 72 x serum creatinine in
 mg/dL

 -  Metabolic function: Calcium, Magnesium, Phosphate, and Potassium levels within
 institutional normal limits.

 -  Hepatic function: Bilirubin less than or equal to 1.5 x ULN. AST and ALT less
 than or equal to 3 ULN and alkaline phosphatase less than or equal to 2.5 x ULN.

 -  Patients must have signed an approved informed consent and authorization permitting
 release of personal health information.

 -  Patients of childbearing potential must have a negative serum pregnancy test prior to
 the study entry and be practicing an effective form of contraception. The effects of
 Nivolumab on the developing human fetus are unknown. For this reason and because other
 therapeutic agents or modalities used in this trial are known to be teratogenic, women
 of child-bearing potential must agree to use adequate contraception (hormonal or
 barrier method of birth control; abstinence) prior to study entry, through the
 duration of study participation and for a period of 5 months after the last dose of
 nivolumab. Should a woman become pregnant or suspect she is pregnant while
 participating in this study, she should inform her treating physician immediately.

 Exclusion Criteria:

 -  The patient is lactating or pregnant

 -  The colposcopy is inadequate; the entire transformation zone is not visualized and
 endocervical curettage is positive for high-grade dysplasia

 -  Clinical concern for invasive cervical cancer

 -  Patients must not have received any prior oncology vaccine therapy

 -  Intercurrent medical illnesses that would impair patient tolerance to participation

 -  Any concurrent medical condition requiring the use of systemic steroids is not
 permitted (the use of inhaled or topic steroids is permitted)

 -  Concurrent treatment with chemotherapy, radiation therapy or immunotherapy for
 intercurrent illnesses

 -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
 may increase the risk associated with study participation or study drug
 administration, impair the ability of the subject to receive protocol therapy, or
 interfere with the interpretation of study results;

 -  Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any
 other antibody or drug specifically targeting T-cell co-stimulation or immune
 checkpoint pathways;

 -  Subjects with an active, known or suspected autoimmune disease. Subjects with type I
 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
 (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or
 conditions not expected to recur in the absence of an external trigger are permitted
 to enroll;

 -  Subjects with interstitial lung disease that is symptomatic or may interfere with the
 detection or management of suspected drug-related pulmonary toxicity

 -  Subjects with history of life-threatening toxicity, including hypersensitivity
 reaction, related to prior immunoglobulin treatment for another condition or any other
 study drug component.

 -  History or evidence upon physical/neurological examination of other central nervous
 system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately
 controlled by medication or considered not potentially interfering with protocol
 treatment;

 -  Surgical procedure <7 days prior to study treatment, vascular access device no
 restriction;

 -  Subjects unable (e.g., due to pacemaker or ICD device) or unwilling to have a
 contrast-enhanced MRI of the head;

 -  History of allergy or hypersensitivity to study drug components

 -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
 days of study drug administration. Inhaled or topical steroids, and adrenal
 replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
 active autoimmune disease.