Carcinoma Cervix,Stage IIIPhase 3NELCERNCT03256916
Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix
A Phase 3 study testing Nelfinavir, Cisplatin and Pelvic EBRT and Brachytherapy in people with Carcinoma Cervix,Stage III, run by Tata Memorial Hospital at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Carcinoma Cervix,Stage III
- What is being tested?
- Nelfinavir, Cisplatin and Pelvic EBRT and Brachytherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- 1 siteIndia
- Study dates
- 16 Jan 2018to 28 May 2024
- Phase
- Phase 3
- 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 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG 0 to 2
- FIGO 2018 Stage IIIA (TNM stage T3a N0 M0) FIGO 2018 Stage IIIB (TNM stage T3b N0 M0) FIGO 2018 Stage IIIC (TNM stage Any T N1 M0)
- No previous irradiation to the pelvis or chemotherapy
- Age 18 years and above
- 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
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- 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
Who cannot join
- Patients with newly diagnosed diabetes , uncontrolled DM (patient with HbA1c of \> 6.5% or FBS value or BSF\>=126 mg/dL respectively on primary evaluation)
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Randomized Clinical Trial to Study the Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Uterine Cervix.
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).
Read the detailed description
The trial is a single centre open label randomized unblinded phase-III study to evaluate the efficacy of an investigational drug (Nelfinavir) in combination with standard therapy consisting of weekly cisplatin and pelvic EBRT in cohort of patients diagnosed with FIGO 2018 stage III Carcinoma cervix.
Patient registration / randomization procedure
348 Patients will be accrued from the Gynaec Oncology Service of Tata Memorial Centre, Mumbai. A study coordinator at TMC will coordinate the accrual and study process and ensure prompt accrual and proper documentation. Eligibility will be checked based on the selection criteria and written informed consent will be obtained prior to randomization. Patients will be given appropriate time to decide for participation. Randomization will be based on a chart prepared with the help of software using a random sorting algorithm. A screening log will be maintained and include the details of all patients screened.
There are two study arms. In Experimental arm (Nelfinavir arm) 174 patients will be accrued \& in Control arm (Standard Arm) 174 patients will be accrued.
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 (chemoradiation \& brachytherapy)
Therapeutic regimens
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.
Nelfinavir
Nelfinavir will be taken orally with food, because the bioavailability increases under the influence of food. Treatment will start 5-7 days before start of chemo radiation and will continue for the duration of external beam radiotherapy ( no Nelfinavir on weekends or radiation breaks). We will be using a dose of 1250mg BID along with weekly cisplatin, 40mg /m2. All patients will undergo blood sugar evaluation, ECG and Lipid Profile at baseline, treatment completion and at 6 months of follow up. Blood sugars will also be monitored at every 2 weeks while on chemoradiation.
Administration of Pelvic EBRT and Brachytherapy
All patients will undergo baseline MRI of abdomen and pelvis (T2+ T1 with and without contrast+ diffusion and perfusion MRI). Extra sequence acquisition as part of research (like BOLD MRI will be performed on only 60 patients ( 30 in each arm). As MRI will be used for response assessment and brachytherapy planning, in addition to axial images saggital and coronal images will be obtained at each examination. 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 45- 50Gy/23-25 #/5 weeks, and involved nodes will receive a total EBRT dose of 55 - 60Gy. 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. Biopsies will be performed at two different time points. One prior to treatment initiation and another before last dose of concurrent cisplatin. Patients will be evaluated by the concerned investigators on a weekly basis during radiation therapy and all the toxicities will be documented according to the CTCAE V4.0.
All patients will undergo image based brachytherapy. Standard guidelines for reporting or prescription will be followed.
Translational research studies
Five ml blood sample and tumor biopsies will be taken prior to nelfinavir use, and after EBRT on the day of 1st ICRT. Phosphorylated Akt and total Akt will be determined using flowcytometry/western blot method, as a marker of penetration of the drug into the tumor. The level of phosphorylated Akt will be correlated with tumour response as measured by PET/CT \& MRI (changes in SUV max as measured by PET and perfusion changes in the tumour as measured by CT scan and tumour reduction in MRI). Akt levels will be measured in the first 60 patients (30 patient cohorts in each arm) both in the lymphocytes and in the tumour tissue.
Multi functional PET and MRI will be done in the first 30 patients of each arm to gain insight in changes in tumor SUV max and hypoxia following treatment with nelfinavir.
This trial represents a unique opportunity to test various hypotheses in the context of future translational research hence tumour biopsy samples will be stored in the clinical biology lab at ACTREC for future biomarker studies. To test various hypothesis we will require frozen tissues prior to and after treatment. In this case each patient will be her own control. Therefore during the time of the first biopsy we will keep some frozen material in liquid nitrogen.
Pharmacokinetic studies
Population pharmacokinetics of nelfinavir will be studied in the group of patients receiving Nelfinavir. For this, sparse sampling strategy will be followed. A random grouping table will be generated by the epidemiology and clinical trials unit and patient will be allotted to one of the groups for pharmacokinetic sampling. Patients will be allotted to one of the five groups sequentially. Four blood samples will be collected from each patient 7-10 days after the start of Nelfinavir. Timing of Blood sample would be based on the group in which the patient is. The sampling time points are so selected to cover the interval of drug administration. In addition one more blood sample will be collected before the last dose of administration of Cisplatin.
- Conditions
- Carcinoma Cervix,Stage III
- Being tested
- Nelfinavir, Cisplatin, Pelvic EBRT and Brachytherapy
- Keywords
- Cervical cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NelfinavirDrug
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.
CisplatinDrug
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.
Pelvic EBRT and BrachytherapyRadiation
Also called Radiation Therapy
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 45- 50Gy/23-25 #/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.
| Study group | Role | What they receive |
|---|---|---|
| Nelfinavir Arm | Experimental | 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 (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 \& ICRT 7Gy X4 # will be given. Receives: Drug: Nelfinavir; Drug: Cisplatin; Radiation: Pelvic EBRT and Brachytherapy |
| Standard Arm | Other | If patient is randomized to standard arm (Cisplatin +Pelvic EBRT and Brachytherapy).
In this patient will receive Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 \& ICRT 7Gy X4 # Receives: Drug: Cisplatin; Radiation: Pelvic EBRT and Brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in 3 year disease free survival
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).
Measured: 3 years
Secondary outcomes (8)
Change in locoregional control rates at 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).
Measured: 3 years
Overall survival at 5 years
Overall survival at 5 years in test and control arms.
Measured: 5 years
Incidence of grade 3/4 adverse events
Incidence of grade 3/4 adverse events in patients with advanced carcinoma of cervix and receiving Nelfinavir along with standard chemoradiation (Cisplatin and Radiotherapy)
Measured: 5 years
Changes in Akt levels in the tumor
Changes in Akt levels in the tumor from pre Nelfinavir to post EBRT.
Measured: 5 years
Change in tumour hypoxia using multifunctional PET/ MRI.
Change in tumour hypoxia using multifunctional PET/ MRI.
Measured: 5 years
Interindividual variability of Volume of distribution
Cmax (Maximum concentration) will be estimated
Measured: 5 years
Interindividual variability of Clearance of nelfinavir.
Clearence (litres per hour)
Measured: 5 years
Interindividual variability of Clearence of Nelfinavir
Half Life (hrs)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start16 Jan 2018
- Primary completion28 May 2024
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Carcinoma Cervix,Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 348 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Supriya Sastri (chopra), Tata Memorial Hospital
- Investigators
- Dr. Supriya J Sastri, MD, Principal investigator, Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03256916
- Sponsor's protocol ID
- TMH Project 1543
- Acronym
- NELCER
- Status last verified
- Jan 2026
- First submitted
- 31 Jul 2017
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diehl JA, Cheng M, Roussel MF, Sherr CJ. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998 Nov 15;12(22):3499-511. doi: 10.1101/gad.12.22.3499.
PubMed 9832503Koumenis C. ER stress, hypoxia tolerance and tumor progression. Curr Mol Med. 2006 Feb;6(1):55-69. doi: 10.2174/156652406775574604.
PubMed 16472113Toulany M, Kasten-Pisula U, Brammer I, Wang S, Chen J, Dittmann K, Baumann M, Dikomey E, Rodemann HP. Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res. 2006 Jul 1;12(13):4119-26. doi: 10.1158/1078-0432.CCR-05-2454.
PubMed 16818713Gupta AK, McKenna WG, Weber CN, Feldman MD, Goldsmith JD, Mick R, Machtay M, Rosenthal DI, Bakanauskas VJ, Cerniglia GJ, Bernhard EJ, Weber RS, Muschel RJ. Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res. 2002 Mar;8(3):885-92.
PubMed 11895923Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. doi: 10.1056/NEJM199904153401503.
PubMed 10202166Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.
PubMed 10202165Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.
PubMed 10202164Choe G, Horvath S, Cloughesy TF, Crosby K, Seligson D, Palotie A, Inge L, Smith BL, Sawyers CL, Mischel PS. Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res. 2003 Jun 1;63(11):2742-6.
PubMed 12782577Kim DW, Huamani J, Fu A, Hallahan DE. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):38-46. doi: 10.1016/j.ijrobp.2005.02.008.
PubMed 16377414Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, Hagan MP, Grant S, Schmidt-Ullrich R. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res. 2003 Mar;159(3):283-300. doi: 10.1667/0033-7587(2003)159[0283:sariao]2.0.co;2.
PubMed 12600231Mathur SP, Mathur RS, Young RC. Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. Am J Reprod Immunol. 2000 Oct;44(4):222-30. doi: 10.1111/j.8755-8920.2000.440406.x.
PubMed 11076094Lee CM, Fuhrman CB, Planelles V, Peltier MR, Gaffney DK, Soisson AP, Dodson MK, Tolley HD, Green CL, Zempolich KA. Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines. Clin Cancer Res. 2006 Jan 1;12(1):250-6. doi: 10.1158/1078-0432.CCR-05-1084.
PubMed 16397049Chopra S, Goda JS, Mittal P, Mulani J, Pant S, Pai V, Kannan S, Deodhar K, Krishnamurthy MN, Menon S, Charnalia M, Shah S, Rangarajan V, Gota V, Naidu L, Sawant S, Thakkar P, Popat P, Ghosh J, Rath S, Gulia S, Engineer R, Mahantshetty U, Gupta S. Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial. BMJ Open. 2022 Apr 6;12(4):e055765. doi: 10.1136/bmjopen-2021-055765.
PubMed 35387819
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Clinical Trial to Study the Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Uterine Cervix.
- ClinicalTrials.gov ID
- NCT03256916
- Acronym / sponsor ID
- NELCER / TMH Project 1543
- Conditions
- Carcinoma Cervix,Stage III
- Keywords
- Cervical cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 348 participants (actual)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- 16 Jan 2018 (actual)
- Primary completion
- 28 May 2024 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The trial is a single centre open label randomized unblinded phase-III study to evaluate the efficacy of an investigational drug (Nelfinavir) in combination with standard therapy consisting of weekly cisplatin and pelvic EBRT in cohort of patients diagnosed with FIGO 2018 stage III Carcinoma cervix.
Patient registration / randomization procedure
348 Patients will be accrued from the Gynaec Oncology Service of Tata Memorial Centre, Mumbai. A study coordinator at TMC will coordinate the accrual and study process and ensure prompt accrual and proper documentation. Eligibility will be checked based on the selection criteria and written informed consent will be obtained prior to randomization. Patients will be given appropriate time to decide for participation. Randomization will be based on a chart prepared with the help of software using a random sorting algorithm. A screening log will be maintained and include the details of all patients screened.
There are two study arms. In Experimental arm (Nelfinavir arm) 174 patients will be accrued \& in Control arm (Standard Arm) 174 patients will be accrued.
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 (chemoradiation \& brachytherapy)
Therapeutic regimens
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.
Nelfinavir
Nelfinavir will be taken orally with food, because the bioavailability increases under the influence of food. Treatment will start 5-7 days before start of chemo radiation and will continue for the duration of external beam radiotherapy ( no Nelfinavir on weekends or radiation breaks). We will be using a dose of 1250mg BID along with weekly cisplatin, 40mg /m2. All patients will undergo blood sugar evaluation, ECG and Lipid Profile at baseline, treatment completion and at 6 months of follow up. Blood sugars will also be monitored at every 2 weeks while on chemoradiation.
Administration of Pelvic EBRT and Brachytherapy
All patients will undergo baseline MRI of abdomen and pelvis (T2+ T1 with and without contrast+ diffusion and perfusion MRI). Extra sequence acquisition as part of research (like BOLD MRI will be performed on only 60 patients ( 30 in each arm). As MRI will be used for response assessment and brachytherapy planning, in addition to axial images saggital and coronal images will be obtained at each examination. 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 45- 50Gy/23-25 #/5 weeks, and involved nodes will receive a total EBRT dose of 55 - 60Gy. 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. Biopsies will be performed at two different time points. One prior to treatment initiation and another before last dose of concurrent cisplatin. Patients will be evaluated by the concerned investigators on a weekly basis during radiation therapy and all the toxicities will be documented according to the CTCAE V4.0.
All patients will undergo image based brachytherapy. Standard guidelines for reporting or prescription will be followed.
Translational research studies
Five ml blood sample and tumor biopsies will be taken prior to nelfinavir use, and after EBRT on the day of 1st ICRT. Phosphorylated Akt and total Akt will be determined using flowcytometry/western blot method, as a marker of penetration of the drug into the tumor. The level of phosphorylated Akt will be correlated with tumour response as measured by PET/CT \& MRI (changes in SUV max as measured by PET and perfusion changes in the tumour as measured by CT scan and tumour reduction in MRI). Akt levels will be measured in the first 60 patients (30 patient cohorts in each arm) both in the lymphocytes and in the tumour tissue.
Multi functional PET and MRI will be done in the first 30 patients of each arm to gain insight in changes in tumor SUV max and hypoxia following treatment with nelfinavir.
This trial represents a unique opportunity to test various hypotheses in the context of future translational research hence tumour biopsy samples will be stored in the clinical biology lab at ACTREC for future biomarker studies. To test various hypothesis we will require frozen tissues prior to and after treatment. In this case each patient will be her own control. Therefore during the time of the first biopsy we will keep some frozen material in liquid nitrogen.
Pharmacokinetic studies
Population pharmacokinetics of nelfinavir will be studied in the group of patients receiving Nelfinavir. For this, sparse sampling strategy will be followed. A random grouping table will be generated by the epidemiology and clinical trials unit and patient will be allotted to one of the groups for pharmacokinetic sampling. Patients will be allotted to one of the five groups sequentially. Four blood samples will be collected from each patient 7-10 days after the start of Nelfinavir. Timing of Blood sample would be based on the group in which the patient is. The sampling time points are so selected to cover the interval of drug administration. In addition one more blood sample will be collected before the last dose of administration of Cisplatin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Nelfinavir Arm | Experimental | Drug: Nelfinavir, Drug: Cisplatin, Radiation: Pelvic EBRT and BrachytherapyIf 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 (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 \& ICRT 7Gy X4 # will be given. |
| Standard Arm | Other | Drug: Cisplatin, Radiation: Pelvic EBRT and BrachytherapyIf patient is randomized to standard arm (Cisplatin +Pelvic EBRT and Brachytherapy). In this patient will receive Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 \& ICRT 7Gy X4 # |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ECOG 0 to 2
- FIGO 2018 Stage IIIA (TNM stage T3a N0 M0) FIGO 2018 Stage IIIB (TNM stage T3b N0 M0) FIGO 2018 Stage IIIC (TNM stage Any T N1 M0)
- No previous irradiation to the pelvis or chemotherapy
- Age 18 years and above
- Ability to tolerate full course of pelvic radiotherapy and brachytherapy
Key exclusion criteria (16 listed)
- Patients with newly diagnosed diabetes , uncontrolled DM (patient with HbA1c of \> 6.5% or FBS value or BSF\>=126 mg/dL respectively on primary evaluation)
- Pts on any drugs which has pharmacological interaction with nelfinavir:
- Pregnant or lactating
- Active co existing malignancy.
- HIV positive patients will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NelfinavirNelfinavir (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 | Nelfinavir Arm |
| CisplatinCisplatin 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. | Drug | Nelfinavir Arm, Standard Arm |
| Pelvic EBRT and BrachytherapyAlso: Radiation TherapyPelvic 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 45- 50Gy/23-25 #/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. | Radiation | Nelfinavir Arm, Standard Arm |
Primary outcome
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).
8 secondary outcomes
Change in locoregional control rates at 3 years
Time frame: 3 years
Overall survival at 5 years
Time frame: 5 years
Incidence of grade 3/4 adverse events
Time frame: 5 years
Changes in Akt levels in the tumor
Time frame: 5 years
Change in tumour hypoxia using multifunctional PET/ MRI.
Time frame: 5 years
Interindividual variability of Volume of distribution
Time frame: 5 years
Interindividual variability of Clearance of nelfinavir.
Time frame: 5 years
Interindividual variability of Clearence of Nelfinavir
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Background: PubMed 9832503Diehl JA, Cheng M, Roussel MF, Sherr CJ. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998 Nov 15;12(22):3499-511. doi: 10.1101/gad.12.22.3499.
- Background: PubMed 16472113Koumenis C. ER stress, hypoxia tolerance and tumor progression. Curr Mol Med. 2006 Feb;6(1):55-69. doi: 10.2174/156652406775574604.
- Background: PubMed 16818713Toulany M, Kasten-Pisula U, Brammer I, Wang S, Chen J, Dittmann K, Baumann M, Dikomey E, Rodemann HP. Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res. 2006 Jul 1;12(13):4119-26. doi: 10.1158/1078-0432.CCR-05-2454.
- Background: PubMed 11895923Gupta AK, McKenna WG, Weber CN, Feldman MD, Goldsmith JD, Mick R, Machtay M, Rosenthal DI, Bakanauskas VJ, Cerniglia GJ, Bernhard EJ, Weber RS, Muschel RJ. Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res. 2002 Mar;8(3):885-92.
- Background: PubMed 10202166Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. doi: 10.1056/NEJM199904153401503.
- Background: PubMed 10202165Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.
- Background: PubMed 10202164Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.
- Background: PubMed 12782577Choe G, Horvath S, Cloughesy TF, Crosby K, Seligson D, Palotie A, Inge L, Smith BL, Sawyers CL, Mischel PS. Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res. 2003 Jun 1;63(11):2742-6.
- Background: PubMed 16377414Kim DW, Huamani J, Fu A, Hallahan DE. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):38-46. doi: 10.1016/j.ijrobp.2005.02.008.
- Background: PubMed 12600231Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, Hagan MP, Grant S, Schmidt-Ullrich R. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res. 2003 Mar;159(3):283-300. doi: 10.1667/0033-7587(2003)159[0283:sariao]2.0.co;2.
- Background: PubMed 11076094Mathur SP, Mathur RS, Young RC. Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. Am J Reprod Immunol. 2000 Oct;44(4):222-30. doi: 10.1111/j.8755-8920.2000.440406.x.
- Background: PubMed 16397049Lee CM, Fuhrman CB, Planelles V, Peltier MR, Gaffney DK, Soisson AP, Dodson MK, Tolley HD, Green CL, Zempolich KA. Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines. Clin Cancer Res. 2006 Jan 1;12(1):250-6. doi: 10.1158/1078-0432.CCR-05-1084.
- Rosser, C.J., et al. Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation. Cancer Gene Ther 11, 273-279 (2004).Link provided by the sponsor.
- Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation forlocally advanced rectal cancer. Radiotherapy and Oncology. 107 ,184-188 (2013).Link provided by the sponsor.
- A Phase I Trial of the HIV Protease Inhibitor Nelfinavir with Concurrent Chemoradiotherapy (CT-RT) for Unresectable Stage IIA/IIIB NSCLC: A Report of Toxicities and Clinical Response. J Thoracic Oncol. ; 7(4): 709-715(2012).Link provided by the sponsor.
- Vijapurkar, U., Kim, M.S. \& Koland, J.G. Roles of mitogen-activated protein kinase and phosphoinositide 3'-kinase in ErbB2/ErbB3 coreceptor-mediated heregulin signaling. Exp Cell Res 284, 291-302 (2003).Link provided by the sponsor.
- Ma, Y.Y., et al. PIK3CA as an oncogene in cervical cancer. Oncogene 19, 2739-2744 (2000).Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Supriya J Sastri, MD principal investigator
Tata Memorial Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nelfinavir, Cisplatin and Pelvic EBRT and Brachytherapy in people with Carcinoma Cervix,Stage III, run by Tata Memorial Hospital at 1 site in India.
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 9 inclusion and 16 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 24 Feb 2026. 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 India. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Improvement in 3 year disease free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03256916, which also lists 13 linked publications.
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 24 Feb 2026.