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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01925378
Recruitment Status : Withdrawn (The study is going to open in a new site)
First Posted : August 19, 2013
Last Update Posted : November 12, 2020
Sponsor:
Information provided by (Responsible Party):
Joseph Anthony Lucci III, The University of Texas Health Science Center, Houston

Brief Summary:
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 or disease Intervention/treatment Phase
Cervical Dysplasia Drug: Nelfinavir Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : November 7, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 ]

    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 :
  1. targeted mechanism of NFV in histological response [ Time Frame: 24 weeks ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01925378


Locations
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United States, Texas
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
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Principal Investigator: Joseph A Lucci, MD The University of Texas Health Science Center, Houston
Publications:
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Responsible Party: Joseph Anthony Lucci III, Professor and Director Division of Gynecologic Oncology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01925378    
Other Study ID Numbers: 20110917-01
First Posted: August 19, 2013    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joseph Anthony Lucci III, The University of Texas Health Science Center, Houston:
Cervical Dysplasia
Additional relevant MeSH terms:
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Cervical Intraepithelial Neoplasia
Uterine Cervical Dysplasia
Neoplasms
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases
Nelfinavir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents