Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix

NCT03256916 | Completed Phase 3 DMC

• 1 other identifier: TMH Project 1543
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 1

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).

Conditions

Carcinoma Cervix,Stage III

Keywords

Cervical cancer

Outcome Measures

Primary Outcomes (1)

• 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).

  3 years

Secondary Outcomes (8)

• Change in locoregional control rates at 3 years

  3 years

• Overall survival at 5 years

  5 years

• Incidence of grade 3/4 adverse events

  5 years

• Changes in Akt levels in the tumor

  5 years

• Change in tumour hypoxia using multifunctional PET/ MRI.

  5 years

Study Arms (2)

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.

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 #

Drug: Cisplatin; Radiation: Pelvic EBRT and Brachytherapy

Interventions

Nelfinavir DRUG

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.

Nelfinavir Arm

Cisplatin DRUG

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 Arm; Standard Arm

Pelvic EBRT and Brachytherapy RADIATION

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.

Also known as: Radiation Therapy

Nelfinavir Arm; Standard Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Females with Carcinoma of cervix Stage IIIB
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (1)

Tata Memorial Centre

Mumbai, Maharashtra, 400012, India

Location

Related Publications (13)

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• Morris 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.

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  PMID: 12600231 BACKGROUND

• Mathur 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.

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• Lee 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.

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• Chopra 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.

  PMID: 35387819 DERIVED

Related Links

• 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).
• 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).
• 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).
• Ma, Y.Y., et al. PIK3CA as an oncogene in cervical cancer. Oncogene 19, 2739-2744 (2000).

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Nelfinavir; Cisplatin; Brachytherapy; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Dr. Supriya J Sastri, MD

  Tata Memorial Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 22, 2017
• Study Start: January 16, 2018
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: February 24, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)