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Cervical CancerPhase 1NCT01485731

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

A Phase 1 study testing Nelfinavir, Cisplatin and Pelvic External Beam Radiation Therapy in people with Cervical Cancer, run by University of Miami at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Nelfinavir will increase the efficacy of Cisplatin based chemo- radiation therapy for locally advanced cervical cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cervical Cancer
What is being tested?
Nelfinavir, Cisplatin and Pelvic External Beam Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Jan 2012to Feb 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Miami

    Miami, Florida, 33136

Other trials in United States

About this study

Official title: Phase 1 Study of Nelfinavir Added to Cisplatin Chemotherapy Concurrent With Pelvic Radiation for Locally Advanced Cervical Cancer (II-IVA)

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

Read the detailed description

Despite cisplatin chemoradiation, 40-50% of women with locally advanced cervical cancer will die from their disease. The evaluation of new chemoradiation regimens have since included cisplatin to further build on its current success. In one year, Nelfinavir will be off patent and become a potential cost effective therapy. HIV Protease inhibitors are now being explored as potential therapies in oncology. The repositioning of HIV protease inhibitors, specifically nelfinavir in cancer therapeutics, is based on three facts. First, recent studies show that HIV protease inhibitors are established broad-spectrum anti-cancer agents that work through pleiotropic mechanisms such as by down-regulating activated mitogenic signaling pathways, and activating the immune response with Nelfinavir being the most potent [7]. Second, HIV protease inhibitors including nelfinavir can target specific viral antigens. Nelfinavir has been shown to target Human Papilloma Virus (HPV)-transformed cervical carcinoma cells via inhibition of E6-mediated proteosomal degradation of mutant p53 [8]. Thirdly, Nelfinavir has radiosensitizing properties through inhibiting the PI3K/Akt signaling pathway as demonstrated in vivo and in vitro in head and neck and pancreatic cancers models [9].

Nelfinavir is currently being evaluated as a radiosensitizer in head and neck and pancreatic cancers in phase I/II clinical trials. Brunner et al. (2008) recently completed the first phase I trial of nelfinavir added to chemoradiation for locally advanced pancreatic cancer [16]. Investigators treated 12 patients with advanced pancreatic carcinoma with Nelfinavir 1250 mg orally twice daily starting 3 days before radiation therapy and continued until the last day of radiation. They found no significant toxicity attributable to nelfinavir and observed a response rate of 50% versus 30% in historical controls. There were 5 of 12 patients with grade 3 hematologic toxicities (4 with leukopenia and 2 with thrombocytopenia). There were 3 of 12 patients with grade 3 GI toxicity (including abdominal pain, nausea, vomiting). There were no grade 4 drug related toxicities [16]. There were grade 1/ 2 toxicities including hematologic (thrombocytopenia, anemia, neutropenia), gastrointestinal toxicities (nausea, vomiting, diarrhea, abdominal pain), and elevated transaminases which were approximately 70%. Ten of 12 patients completed therapy. Complete responses were observed in 5 patients and partial responses were observed in 5 of 10 patients. Overall, the addition of Nelfinavir added minimal additional toxicity. Determination of a dose for biologic activity was not performed [14].

In summary, HIV protease inhibitors have a very broad spectrum of anti-tumor activity and can inhibit proliferation and/or cause death in the majority of cancer cell lines tested in a dose-dependent manner [7]. Nelfinavir has been found to be the most potent anti-tumor agent among the HIV protease inhibitors. As a result, several clinical trials are investigating Nelfinavir as a chemotherapeutic agent with and without concurrent radiation therapy in varied disease sites including rectal, head \& neck, glioblastomas, pancreas, renal cell, non-small cell lung cancer, liposarcoma, and gliomas. The NCI is also investigating Nelfinavir as single agent chemotherapy in advanced and recurrent solid tumors [15].

As Nelfinavir has both cytotoxic and radiation sensitizing effects, it is an ideal agent to use in combination with cisplatin-based chemoradiation in locally advanced cervical cancers.

In this study, patients with clinical stages IIA, IIB, IIIA, IIIB, IVA cervical carcinoma limited to the pelvis will receive twice daily oral Nelfinavir (NFV) and weekly IV cisplatin in combination as radiosensitizers with daily whole pelvic external beam (Mon-Fri) followed by intracavitary radiation brachytherapy.

Conditions
Cervical Cancer
Being tested
Nelfinavir, Cisplatin, Pelvic External Beam Radiation Therapy, Brachytherapy, Pharmacokinetic Sampling
Keywords
Cervical, Cancer, Uterine Cervix, Squamous Cell, Adenocarcinoma
Medical subject headings
Uterine Cervical Neoplasms, Neoplasms, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NelfinavirDrug

    Also called NFV

    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

  • CisplatinDrug

    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 TherapyRadiation

    Also called PEBRT

    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.

  • BrachytherapyRadiation

    Also called BT

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

  • Pharmacokinetic SamplingProcedure or surgery

    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.

  • Cervical BiopsyProcedure or surgery

    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

  • Pelvic ExaminationProcedure or surgery

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

  • Pap SmearProcedure or surgery

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

  • AudiogramProcedure or surgery

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

  • ProctoscopyProcedure or surgery

    Optional. Pre-Treatment

  • CytoscopyProcedure or surgery

    Optional. Pre-Treatment

  • Renal UltrasoundProcedure or surgery

    Optional. Pre-Treatment

  • CT ScanProcedure or surgery

    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)

  • Whole Body PET/CT ScanProcedure or surgery

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

Study groups in NCT01485731
Study groupRoleWhat they receive
Nelfinavir + Cisplatin + Pelvic Radiation TherapyExperimentalNelfinavir in combination with Cisplatin and Pelvic Radiation Therapy
Receives: Drug: Nelfinavir; Drug: Cisplatin; Radiation: Pelvic External Beam Radiation Therapy; Radiation: Brachytherapy; Procedure: Pharmacokinetic Sampling; Procedure: Cervical Biopsy; Procedure: Pelvic Examination; Procedure: Pap Smear; Procedure: Audiogram; Procedure: Proctoscopy; Procedure: Cytoscopy; Procedure: Renal Ultrasound; Procedure: CT Scan; Procedure: Whole Body PET/CT Scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3 Years

  2. 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.

    Measured: 3 Years

Secondary outcomes (4)
  1. Serum Levels of Nelfinavir and other Biomarker Activity

    To determine the levels of Akt activity (and downstream effectors such as pGSK3, pEBP1) and p16INK4A in addition to the presence of Human Papilloma Virus (HPV) 16 and18,and E6/E7 RNA in cervical biopsy specimens of patients at three different time points (1. pre-nelfinavir, pre-radiation, 2. while on nelfinavir, pre-radiation, 3. at completion of radiation therapy), and correlate the levels of these markers to serum Nelfinavir levels from blood drawn at the day of the biopsy.

    Measured: 3 Years

  2. Response to protocol therapy

    Tumor response to protocol therapy will be measured using Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

    Measured: 3 years

  3. Progression-free Survival

    Progression-Free Survival is the period from start of treatment until documented disease progression or death from any cause. For surviving patients without progression, progression-free survival will be censored at the last date of documented progression-free status.

    Measured: 3 years

  4. Overall Survival

    Survival is the observed length of life from start of treatment to death. For surviving patients, follow-up will be censored at the date of last contact.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2011 (estimated)
  2. Study startJan 2012
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01485731
Sponsor's protocol ID
20100153
Status last verified
Jun 2015
First submitted
29 Nov 2011
Last updated
3 Jun 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nelfinavir, Cisplatin and Pelvic External Beam Radiation Therapy in people with Cervical Cancer, run by University of Miami at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients with Adverse Events in Phase 1 Study of Nelfinavir + Cisplatin + Pelvic Radiation Therapy (time frame: 3 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2015.

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