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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A PHASE II SINGLE-ARM INTERVENTION TRIAL OF NELFINAVIR IN PATIENTS WITH GRADE 2/3 or 3 CERVICAL INTRAEPITHELIAL NEOPLASIA

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.

Detailed Summary:

2.0 BACKGROUND AND RATIONALE 2.1 Cervical Cancer Etiology and Targets for Intervention Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Implementation of widespread screening has created drastic improvements in the incidence of cervical cancer as well as significant decreases in mortality over the last 30 years. It is estimated that in 2011, there will be 12,710 women in the US diagnosed with cervical cancer and ultimately 4,290 women will die from the disease. Cervical cancer is unique in that there exists a well-defined pre-malignant phase, referred to as cervical dysplasia, which can be suspected on cytological examination (pap smear) of exfoliated cervical cells and confirmed on histological examination of cervical biopsy material. The pre-cancerous changes represent a spectrum of histological abnormalities or cervical intraepithelial neoplasia (CIN) ranging from CIN 1 (mild dysplasia) to CIN2 (moderate dysplasia) to CIN3 (severe dysplasia/ carcinoma in situ). The timeline of progression for CIN 3 to invasive cancer in untreated women averages between 8.1 and 12.6 years.The surgical treatment of cervical pre-cancerous is therapeutically efficacious. However, it is an invasive procedure which has been associated with fertility and obstetrical complications in reproductive aged women. An attractive alternative to an excisional or ablative procedure would be to utilize an agent which could be applied topically or taken by mouth to foster regression of cervical dysplasia. The use of natural, synthetic, or biologic chemical agents to reverse, suppress, or prevent carcinogenic progression is called chemoprevention.

A prerequisite for cervical cancer is persistent infection by a high-risk human papillomavirus allowing viral gene products sufficient time with which to induce carcinogenesis through a generally well understood natura
Sponsor: Joseph Anthony Lucci III

Current Primary Outcome: 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.



Original Primary Outcome: Same as current

Current Secondary Outcome: 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


Original Secondary Outcome: Same as current

Information By: The University of Texas Health Science Center, Houston

Dates:
Date Received: April 30, 2013
Date Started: July 2012
Date Completion: December 2022
Last Updated: February 22, 2017
Last Verified: February 2017