Safety Study of Nelfinavir + Cisplatin + Pelvic Radiation Therapy to Treat Cervical Cancer

Summary

Nelfinavir will increase the efficacy of Cisplatin based chemo- radiation therapy for locally advanced cervical cancer.

Conditions

• Cervical Cancer

Interventions

DRUG

Nelfinavir

Nelfinavir (NFV) will be prescribed orally twice daily for 7 days prior to initiation of cisplatin and pelvic radiation at the starting dose level, 875 mg BID

DRUG

Cisplatin

Cisplatin at 40 mg/m2 (maximum total dose of 70 mg per week), will be infused intravenously once per week on either Day 1, 2, 3, 4, or 5 of weeks 2 to 6, preferably approximately four hours prior to radiation therapy. One additional cycle of cisplatin will be given either week 7 or 8 for a total of 6 cycles of cisplatin. Patients are not to be dosed more than 70 mg/week.

RADIATION

Pelvic External Beam Radiation Therapy

Pelvic external beam radiation therapy (PEBRT) will be delivered in combination with weekly IV cisplatin (40mg/mg2) and twice daily oral NFV.PEBRT should be delivered once each day during the business week (Monday to Friday) according to the acceptable standards of care as prescribed by the treating radiation oncologist(s). The radiation therapy should consist of whole pelvic external beam radiation therapy (WPEBRT) with or without a parametrial boost (PB). PEBRT will be interdigitated with one administration of intrauterine brachytherapy (BT) given on any business day of week 7 or 8.

RADIATION

Brachytherapy

PEBRT will be interdigitated with one administration of intrauterine brachytherapy (BT) given on any business day of week 7 or 8.

PROCEDURE

Pharmacokinetic Sampling

Serum levels of Nelfinavir will be assayed at the following 3 time points: 5-8 days after initiation of NFV single agent (on Day 5, 6, or 7 of week 1 or day 1 of week 2), 1 week after combined NFV and cisplatin pelvic radiation (on day 15, 16, or 17 if start on Monday) for measurement of steady state, and at the completion of treatment (within the last 3 days of radiation in week 6). Blood samples will be taken before drug administration on the day of the sample to make sure the concentrations are actually at a minimum and before tumor biopsies.

PROCEDURE

Cervical Biopsy

Three punch biopsies of cervical tumor will be obtained during office visit at each time point (for PCR, IHC, and banked for future research). NFV serum levels will be obtained once NFV has been started (day 5-8 pre chemoradiation and at completion of chemoradiation) before each cervical biopsy

PROCEDURE

Pelvic Examination

Pre-Treatment, at the end of treatment +/- 1 week, every 3 months +/- 2 weeks after therapy (x 1 year)

PROCEDURE

Pap Smear

Recommended. Every 3 months +/- 2 weeks after therapy (x 1 year)

PROCEDURE

Audiogram

Required in patients with history of hearing loss; 28 days within starting treatment and every other cycle.

PROCEDURE

Proctoscopy

Optional. Pre-Treatment

PROCEDURE

Cytoscopy

Optional. Pre-Treatment

PROCEDURE

Renal Ultrasound

Optional. Pre-Treatment

PROCEDURE

CT Scan

CT Scan of Chest/Abdomen/Pelvis, pre-treatment,Immediately at end of trial +/- 1 week, Every 3 months +/- 2 weeks after therapy (x 1 year)

PROCEDURE

Whole Body PET/CT Scan

In lieu of CT Scan, pre-treatment,Immediately at end of trial +/- 1 week, Every 3 months +/- 2 weeks after therapy (x 1 year)

Sponsors & Collaborators

• University of Miami

  lead OTHER

Principal Investigators

• J. Matthew Pearson, MD · University of Miami

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2015-02-28

Completion

2015-02-28

Countries

• United States

Study Locations