A Phase II Single-arm Intervention Trial of Nelfinavir in Patients With Grade 2/3 or 3 Cervical Intraepithelial Neoplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Joseph Lucci, University of Miami
ClinicalTrials.gov Identifier:
NCT01925378
First received: April 30, 2013
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

Preliminary data showed that Nelfinavir has selective apoptotic effects on HPV+ cervical tumor cell lines. Furthermore, in a Phase I clinical trial, the combination of NFV and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer. Therefore, for the proposed research, the principal investigator will use a single-arm Phase II intervention trial study design with focus on the efficacy of NFV to induce complete or partial remission of CIN 2/3 or CIN 3 as well as biomarker evaluation.


Condition Intervention Phase
Cervical Dysplasia
Drug: Nelfinavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II SINGLE-ARM INTERVENTION TRIAL OF NELFINAVIR IN PATIENTS WITH GRADE 2/3 or 3 CERVICAL INTRAEPITHELIAL NEOPLASIA

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • 1.1 Efficacy of Nelfinavir (NFV) to induce complete remission (or partial regression to CIN 1) of CIN 2/3 or CIN 3 as evaluated in the post-treatment excisional biopsy. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    EVALUATION CRITERIA

    Parameters of response:

    Histologic evaluation of the post-treatment LLETZ/cone specimen.

    (1) Persistent with worst disease being CIN 3; (2) Persistent with worst disease being CIN 2/3; (3) Persistent with worst disease being CIN 2; (4) Persistent with worst disease being CIN 1; (5) Normal tissue; no evidence of CIN present; (6) Squamous cell carcinoma, in situ.

    Histologic Complete Response will be judged as complete absence of any histologic evidence of CIN in the biopsy or LLETZ .

    Histologic Partial Response will be judged as regression of CIN 2/3 or CIN 3 to persistent disease with worst grade being CIN 1 in the LLETZ cone biopsy.

    Histologic Persistent Disease will be defined as evidence of CIN 2, CIN 2/3 or CIN 3 in the LLETZ/cone biopsy.

    Histologic Progression: Evidence of disease progression such as invasive carcinoma.



Secondary Outcome Measures:
  • targeted mechanism of NFV in histological response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Pathway inhibition will be demonstrated when there is a decrease of PI3K and/or Akt on IHC between the enrollment biopsy and the final biopsy or the LLETZ/cone specimen


Estimated Enrollment: 30
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nelfinavir
This is a single arm intervention trial of nelfinavir in women with grade 2/3 or grade 3 cervical intraepithelial neoplasia
Drug: Nelfinavir

All medications which a patient is taking will be reviewed at each visit, including the screening, day 1, weeks 4,12, 24.

All patients enrolled in the study will receive 1,250 mg twice PO daily for a 24 week duration.

Other Name: Viracept

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a Cytology report with a High Grade Squamous Intra Epithelial Lesion "HSIL" or have histologically proven CIN 2/3 or CIN 3 diagnosed by cervical biopsy between 2 and 8 weeks prior to enrollment. For a patient to be eligible, the Cytology report must state High Grade Squamous Intra Epithelial Lesion "HSIL" or the pathology report must clearly state "CIN 2/3" or "CIN 3" or must state "moderate-severe dysplasia", "moderate severe dyskaryosis," "severe dysplasia," or "severe dyskaryosis." Patients with a diagnosis of CIN 2 alone or moderate dysplasia or dyskaryosis alone are not eligible for this study.
  • Patients must be at least 18 years of age.
  • Patients must have a satisfactory (readable, good quality) colposcopic evaluation at least 14 days after diagnostic biopsy.
  • Patients must have colposcopically visible cervical lesion at entry consistent with biopsy.
  • Patients must have a negative urine pregnancy test within 14 days of starting the NFV. Women of childbearing potential must practice an acceptable form of contraception (e.g. intrauterine device, contraceptive pills, diaphragm, condoms).
  • Patients must have a GOG Performance Status of 0, 1, or 2.
  • Patients must be good candidates for delayed treatment of their CIN, i.e. they must be reliable to return for follow-up and provide a combination of at least three phone numbers or addresses for contact.
  • Patients must have adequate*:
  • CBC/Platelets: Hemoglobin (HgB) greater than 10.0g/dl; white blood cell (WBC) count greater than 3000/mcl; Platelet count greater than 125,000/mcl.
  • Renal function: Creatinine less than or equal to 1.5 x Upper Limit Normal (ULN).
  • Hepatic function: Total bilirubin less than or equal to 1.5 x ULN excluding Gilbert's disease; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.0 x ULN.
  • Glycemic control: fasting glucose < 126; random glucose <200; hemoglobin A1C ≤ 7.0%

    *These lab results must be evaluated prior to patient enrollment.

  • Patients must have signed an approved informed consent and authorization permitting release of personal health information.
  • Patients must have a negative HIV test within 14 days of starting the NFV.
  • Patients with allergies or known sensitivity to Nelfinavir will be excluded or withdrawn after treatment, if deemed a safety concern by the principal Investigator.

Exclusion Criteria:

Ineligible Patients

  • Patients who are pregnant or breast-feeding.
  • Patients with cytologic or biopsy evidence of endocervical dysplasia or invasive cancer.
  • Patients with undiagnosed abnormal vaginal bleeding.
  • Patients with a known immunocompromised condition or a positive HIV test. Patients with a prior history of cervical cancer.
  • Patients with a chronic or acute renal, or hepatic disorder, a significant bleeding disorder, or any other condition which in the Investigator's opinion might preclude study participation for the duration of the trial.
  • Patients taking concurrent medication that is metabolized by the CYP3A4 isoenzyme.
  • Patients taking the following concurrent medications: astemizole, cisapride, salmeterol, alfuzosin, terfinadine, amiodarone, midazolam, quinadine, ergot derivatives, pimozide, rifampin, triazolam, warfarin, azithromycin, carbamezpine, cyclosporine, didanosine, fluticasone propionate, phenobarbital, phenytoin, trazadone, sirolimus, tacrolimus , and St. John's wart.
  • Patients who are unwilling, or unable, to practice an acceptable form of contraception (e.g. intrauterine device, contraceptive pills, diaphragm, condoms). For those women who choose to use oral contraceptive pills, they will be encouraged to use a second form of contraception, such as condoms, because of the potential for altered serum levels of oral contraceptives.
  • Patients with uncontrolled diabetes; as defined by hemoglobin A1C ≥ 7.1%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925378

Contacts
Contact: Joseph De La Garza, MD 3052439189 jdelagarza@med.miami.edu
Contact: Sindy Jaramillo 3052432150 sjaramillo@med.miami.edu

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Sindy Jaramillo    305-243-2150    sjaramillo@med.miami.edu   
Contact: Joseph de la Garza, MD    3052439189      
Principal Investigator: Joseph Lucci, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Joseph Lucci, MD University of Miami
  More Information

Publications:
Responsible Party: Joseph Lucci, Professor and Director Division of Gynecologic Oncology, University of Miami
ClinicalTrials.gov Identifier: NCT01925378     History of Changes
Other Study ID Numbers: 20110917-01
Study First Received: April 30, 2013
Last Updated: August 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Cervical Dysplasia

Additional relevant MeSH terms:
Uterine Cervical Dysplasia
Neoplasms
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Nelfinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014