Nivolumab Based Immunotherapy for Treatment of High Grade Cervical Dysplasia

January 17, 2019 updated by: University of Texas Southwestern Medical Center

Phase II Trial of Nivolumab Based Immunotherapy for the 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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1
Nivolumab, 3 mg/kg Iv, day 1
Drug: Nivolumab
Protocol dose: 3mg/kg mg as a 30-minute IV infusion on Day 1 (Arm I) or Days 1, 15, 29 (Arm II).
Other Names:
  • Opdivo, BMS-936558, MDX1106
Active Comparator: Arm 2
Nivolumab, 3 mg/kg IV, days 1, 15, 29
Drug: Nivolumab
Protocol dose: 3mg/kg mg as a 30-minute IV infusion on Day 1 (Arm I) or Days 1, 15, 29 (Arm II).
Other Names:
  • Opdivo, BMS-936558, MDX1106

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of regression on high grade dysplasia lesions
Time Frame: 15 weeks after the beginning of immunotherapy
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

  • Principal Investigator: Jayanthi Lea, MD, Univeristy of Texas Southwestern Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 15, 2019

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

June 1, 2020

Study Registration Dates

First Submitted

January 15, 2019

First Submitted That Met QC Criteria

January 15, 2019

First Posted (Actual)

January 17, 2019

Study Record Updates

Last Update Posted (Actual)

January 18, 2019

Last Update Submitted That Met QC Criteria

January 17, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 032017-028

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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