Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix (NELCER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03256916
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Supriya Sastri (chopra), Tata Memorial Hospital

Brief Summary:

The primary aim of the trial is to study the impact of nelfinavir on 3 year disease free survival in patients with advanced carcinoma of cervix receiving standard chemoradiation (Cisplatin and Radiotherapy).

There will be two study groups. One group will receive standard treatment (concurrent chemoradiation and brachytherapy) & other group will receive nelfinavir 5-7 days prior to standard treatment (chemoradiation & brachytherapy).


Condition or disease Intervention/treatment Phase
Carcinoma Cervix, Stage III Drug: Nelfinavir Drug: Cisplatin Radiation: Pelvic EBRT and Brachytherapy Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: There will be two study arms. If patient is randomized to standard arm patient will receive concurrent chemoradiation and brachytherapy. If patient is randomized to nelfinavir arm then nelfinavir will be started at the dose of 1250 mg bid 5-7 days prior to standard treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Clinical Trial to Study the Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Uterine Cervix.
Actual Study Start Date : January 10, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nelfinavir Arm

If patient is randomized to nelfinavir arm then nelfinavir will be given orally with food at the dose of 1250 mg bid 5-7 days prior to start of chemoradiation.

Then Pelvic EBRT (46Gy /23#/4.5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 # will be given.

Drug: Nelfinavir
Nelfinavir (HIV protease inhibitor) targets proteasome and inhibits AKT phosphorylation and plays an important role in radiosensitization of tumour cells.Nelfinavir will be given to the patient orally with food, because the bioavailability increases under the influence of food.

Drug: Cisplatin
Cisplatin will be administered on a weekly basis with a dose of 40 mg/m2 by IV infusion over a period of 1 hour 2-4 hours prior to start of EBRT. Patient will be premedicated with I.V Ondansetron to prevent emesis. Pre chemotherapy and post chemotherapy, patient will be administered IV fluids for effective renal clearance of cisplatin.

Radiation: Pelvic EBRT and Brachytherapy
Pelvic EBRT will delivered by standard 4 field technique using 6MV/15 MV photon beams. Prior to delivery of radiation, patients will be simulated by CT simulator for planning the beam arrangements. Total dose of pelvic EBRT will be 46Gy/23 #/4.5 weeks. The prescribed dose will be specified according to ICRU 50 guidelines. All patients will be treated with 3D conformal external radiation with target delineation and multileaf collimator leaf shaping.

Standard Arm

If patient is randomized to standard arm (Cisplatin +Pelvic EBRT and Brachytherapy).

In this patient will receive Pelvic EBRT (46Gy /23#/4.5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 #

Drug: Cisplatin
Cisplatin will be administered on a weekly basis with a dose of 40 mg/m2 by IV infusion over a period of 1 hour 2-4 hours prior to start of EBRT. Patient will be premedicated with I.V Ondansetron to prevent emesis. Pre chemotherapy and post chemotherapy, patient will be administered IV fluids for effective renal clearance of cisplatin.

Radiation: Pelvic EBRT and Brachytherapy
Pelvic EBRT will delivered by standard 4 field technique using 6MV/15 MV photon beams. Prior to delivery of radiation, patients will be simulated by CT simulator for planning the beam arrangements. Total dose of pelvic EBRT will be 46Gy/23 #/4.5 weeks. The prescribed dose will be specified according to ICRU 50 guidelines. All patients will be treated with 3D conformal external radiation with target delineation and multileaf collimator leaf shaping.




Primary Outcome Measures :
  1. Improvement in 3 year disease free survival [ Time Frame: 3 years ]
    Improvement in 3 year disease free survival by the addition of Nelfinavir to patients with advanced carcinoma of cervix and receiving standard chemoradiation (Cisplatin and Radiotherapy).


Secondary Outcome Measures :
  1. Change in locoregional control rates at 3 years [ Time Frame: 3 years ]
    Change in locoregional control rates at 3 years by the addition of Nelfinavir to patients with advanced carcinoma of cervix and receiving standard chemoradiation (Cisplatin and Radiotherapy).

  2. Overall survival at 5 years [ Time Frame: 5 years ]
    Overall survival at 5 years in test and control arms.

  3. Incidence of grade 3/4 adverse events [ Time Frame: 5 years ]
    Incidence of grade 3/4 adverse events in patients with advanced carcinoma of cervix and receiving Nelfinavir along with standard chemoradiation (Cisplatin and Radiotherapy)

  4. Changes in Akt levels in the tumor [ Time Frame: 5 years ]
    Changes in Akt levels in the tumor from pre Nelfinavir to post EBRT.

  5. Change in tumour hypoxia using multifunctional PET/ MRI. [ Time Frame: 5 years ]
    Change in tumour hypoxia using multifunctional PET/ MRI.

  6. Interindividual variability of Volume of distribution [ Time Frame: 5 years ]
    Cmax (Maximum concentration) will be estimated

  7. Interindividual variability of Clearance of nelfinavir. [ Time Frame: 5 years ]
    Clearence (litres per hour)

  8. Interindividual variability of Clearence of Nelfinavir [ Time Frame: 5 years ]
    Half Life (hrs)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Females with Carcinoma of cervix Stage IIIB
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • ECOG 0 to 2
  • FIGO Stage III B Carcinoma Cervix
  • No previous irradiation to the pelvis or chemotherapy
  • Age 18 - 65 years
  • Ability to tolerate full course of pelvic radiotherapy and brachytherapy
  • Adequate bone marrow, liver, and kidney function defined as neutrophil count ≥ 1500 platelet count ≥ 100,000, total bilirubin less than 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN, and creatinine less than 1.5 upper limit of normal or Creatinine clearance greater than 60 mL/min/1.73 m2
  • No recent (less than 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
  • Ability to understand and the willingness to sign an informed consent document
  • Should be willing to undergo extra biopsy and blood collection for pharmacokinetic studies

Exclusion criteria

  • Diabetes Mellitus.
  • Pts on any drugs which has pharmacological interaction with nelfinavir:

    • Terfenadine, cisapride, sildenafil, lovastatin or simvastatin and medication that are metabolized by the CYP3A4 isoenzyme.
    • Antiarrhythmics (amiodarone, quinidine).
    • Neuroleptics (pimozide).
    • Sedative/Hypnotic agents (midazolam, triazolam).
    • Ergot derivatives.
    • HMG-CoA reductase inhibitors (atorvastatin).
    • Rifampicin, Rifabutin.
    • Felodipine, Nifedipine.
  • Pregnant or lactating
  • Active co existing malignancy.
  • HIV positive patients will be excluded.
  • Patients with hemophilia.
  • Patients with reduced creatinine clearance ( less than 50 ml/ min) or unilateral or bilateral hydronephrosis will be excluded.
  • History of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256916


Contacts
Layout table for location contacts
Contact: Dr. Supriya J Sastri, MD 9930958309 supriyasastri@gmail.com
Contact: Dr. Jayant Goda, MD 24177000 ext 7027 godajayantsastri@gmail.com

Locations
Layout table for location information
India
Tata Memorial Centre Recruiting
Mumbai, Maharashtra, India, 400012
Contact: Supriya J Sastri, MD    9930958309    supriyasastri@gmail.com   
Contact: Jayant Goda, MD    24177000 ext 7027    godajayantsastri@gmail.com   
Principal Investigator: Supriya J Sastri, MD         
Principal Investigator: Jayant Goda, MD         
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
Layout table for investigator information
Principal Investigator: Dr. Supriya J Sastri, MD Tata Memorial Centre
Additional Information:

Publications:

Layout table for additonal information
Responsible Party: Supriya Sastri (chopra), Principal Investigator, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT03256916    
Other Study ID Numbers: TMH Project 1543
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: March 19, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Supriya Sastri (chopra), Tata Memorial Hospital:
Cervical cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Nelfinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents