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

• Status: Withdrawn
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Joseph Anthony Lucci III; The University of Texas Health Science Center, Houston
• Collaborator: The University of Texas Health Science Center, Houston
• Treatments: Nelfinavir

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%