Nivolumab Based Immunotherapy for Treatment of High Grade Cervical Dysplasia

NCT03808168 | Withdrawn Phase 2 DMC

• 1 other identifier: STU 032017-028
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cervix Uteri--Diseases

Outcome Measures

Primary Outcomes (1)

• Rate of regression on high grade dysplasia lesions

  The endpoints of the current study will be to determine the rate of spontaneous regression on high grade dysplasia lesions

  15 weeks after the beginning of immunotherapy

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

Nivolumab, 3 mg/kg Iv, day 1

Drug: Nivolumab

Arm 2

ACTIVE COMPARATOR

Nivolumab, 3 mg/kg IV, days 1, 15, 29

Drug: Nivolumab

Interventions

Nivolumab DRUG

Protocol dose: 3mg/kg mg as a 30-minute IV infusion on Day 1 (Arm I) or Days 1, 15, 29 (Arm II).

Also known as: Opdivo, BMS-936558, MDX1106

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jayanthi Lea, MD

  Univeristy of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 17, 2019
• Study Start: January 15, 2019
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: January 18, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share