Safety Study of Nelfinavir + Cisplatin + Pelvic Radiation Therapy to Treat Cervical Cancer
Phase 1 Study of Nelfinavir Added to Cisplatin Chemotherapy Concurrent With Pelvic Radiation for Locally Advanced Cervical Cancer (II-IVA)
1 other identifier
interventional
8
1 country
1
Brief Summary
Nelfinavir will increase the efficacy of Cisplatin based chemo- radiation therapy for locally advanced cervical cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2012
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 29, 2011
CompletedFirst Posted
Study publicly available on registry
December 5, 2011
CompletedStudy Start
First participant enrolled
January 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2015
CompletedJune 3, 2015
June 1, 2015
3.1 years
November 29, 2011
June 1, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Patients with Adverse Events in Phase 1 Study of Nelfinavir + Cisplatin + Pelvic Radiation Therapy
Number of Patients with Adverse Events in Phase 1 Study of Nelfinavir + Cisplatin + Pelvic Radiation Therapy
3 Years
The proportion of enrolled patients for whom Nelfinavir dose can be successfully administered in combination with Cisplatin and Pelvic Radiation Therapy.
Maximum tolerable Phase II dose of Nelfinavir in combination with Cisplatin and Pelvic Radiation Therapy.
3 Years
Secondary Outcomes (4)
Serum Levels of Nelfinavir and other Biomarker Activity
3 Years
Response to protocol therapy
3 years
Progression-free Survival
3 years
Overall Survival
3 years
Study Arms (1)
Nelfinavir + Cisplatin + Pelvic Radiation Therapy
EXPERIMENTALNelfinavir in combination with Cisplatin and Pelvic Radiation Therapy
Interventions
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
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.
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.
PEBRT will be interdigitated with one administration of intrauterine brachytherapy (BT) given on any business day of week 7 or 8.
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.
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
Pre-Treatment, at the end of treatment +/- 1 week, every 3 months +/- 2 weeks after therapy (x 1 year)
Recommended. Every 3 months +/- 2 weeks after therapy (x 1 year)
Required in patients with history of hearing loss; 28 days within starting treatment and every other cycle.
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)
In lieu of CT Scan, pre-treatment,Immediately at end of trial +/- 1 week, Every 3 months +/- 2 weeks after therapy (x 1 year)
Eligibility Criteria
You may qualify if:
- All patients with primary, previously untreated, histologically confirmed invasive carcinoma of the uterine cervix (any cell type). Clinical stages IIA, IIB, IIIA, IIIB, IVA.
- Patients must have adequate bone marrow, renal and hepatic function:
- ANC ≥ 1,500/μL;
- Platelet count ≥ 100,000/μL;
- Creatinine \< 2.0 mg/dL;
- Total Bilirubin ≤ 1.5 times normal;
- SGOT ≤ 3 times normal.
- Patients with a GOG Performance Status of 0, 1, or 2.
- Patients with ureteral obstruction must be treated with stent or nephrostomy tube.
- Patients must be entered within eight weeks of diagnosis.
- Patients of childbearing potential must use an effective form of birth control."Patients receiving oral contraceptives should be instructed that alternate or additional contraceptive measures should be used during therapy with VIRACEPT. "
- Seronegative HIV status.
- Patients must be at least 18 years of age.
- Patients must have signed an approved informed consent and authorization permitting release of personal health information.
You may not qualify if:
- Patients with Stage IA, IB or IVB disease.
- Patients who have known metastases to other organs outside the radiation field at the time of the original clinical and surgical staging.
- Patients who have received previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy.
- Patients with septicemia or severe infection.
- Patients who have circumstances that will not permit completion of this study or the required follow-up.
- Patients who are pregnant at the time of diagnosis and do not wish pregnancy termination prior to initiation of treatment.
- Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields.
- Patients with other concomitant malignancies (with the exception of non-melanoma skin cancer), who had (or have) any evidence of other cancer present within the last 5 years.
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
- Patients with poorly controlled diabetes mellitus despite medication.
- Patients taking anti-arrhythmic agents such as amiodarone, quinidine, rifampin, ergot derivatives such as ergotamine, St Johs Wort, HMG-CoA reductase inhibitors such as lovastatin, neuroleptic such as pimozide, sedatives such as midazolam and triazolam among other CYP3A4 and CYP2C19 substrates.
- Patients with Phenylketonuria.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Miami
Miami, Florida, 33136, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
J. Matthew Pearson, MD
University of Miami
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor of Clinical
Study Record Dates
First Submitted
November 29, 2011
First Posted
December 5, 2011
Study Start
January 1, 2012
Primary Completion
February 1, 2015
Study Completion
February 1, 2015
Last Updated
June 3, 2015
Record last verified: 2015-06