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

NCT01925378 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 20110917-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cervical Dysplasia

Keywords

Cervical Dysplasia

Outcome Measures

Primary Outcomes (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.

  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.

  24 weeks

Secondary Outcomes (1)

• targeted mechanism of NFV in histological response

  24 weeks

Study Arms (1)

Nelfinavir

EXPERIMENTAL

This is a single arm intervention trial of nelfinavir in women with grade 2/3 or grade 3 cervical intraepithelial neoplasia

Drug: Nelfinavir

Interventions

Nelfinavir DRUG

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.

Also known as: Viracept

Nelfinavir

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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%

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (7)

• Hampson L, Kitchener HC, Hampson IN. Specific HIV protease inhibitors inhibit the ability of HPV16 E6 to degrade p53 and selectively kill E6-dependent cervical carcinoma cells in vitro. Antivir Ther. 2006;11(6):813-25.

  PMID: 17310826 BACKGROUND

• Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002 Jan 1;97(1):72-81. doi: 10.1002/ijc.1571.

  PMID: 11774246 BACKGROUND

• Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36. doi: 10.3322/caac.20121. Epub 2011 Jun 17.

  PMID: 21685461 BACKGROUND

• Solomon D, Schiffman M, Tarone R; ALTS Study group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001 Feb 21;93(4):293-9. doi: 10.1093/jnci/93.4.293.

  PMID: 11181776 BACKGROUND

• Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res. 1976 Jul;36(7 PT 2):2699-702.

  PMID: 1277177 BACKGROUND

• Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. doi: 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F.

  PMID: 10451482 BACKGROUND

• Zhang L, Epstein JB, Poh CF, Berean K, Lam WL, Zhang X, Rosin MP. Comparison of HPV infection, p53 mutation and allelic losses in post-transplant and non-posttransplant oral squamous cell carcinomas. J Oral Pathol Med. 2002 Mar;31(3):134-41. doi: 10.1034/j.1600-0714.2002.310302.x.

  PMID: 11903818 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Nelfinavir

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joseph A Lucci, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director Division of Gynecologic Oncology

Study Record Dates

• First Submitted: April 30, 2013
• First Posted: August 19, 2013
• Study Start: November 7, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: November 12, 2020

Record last verified: 2020-11

Locations

US (1)