Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Cervix

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).

Timeline

Start

2018-01-16

Primary completion

2024-05-28

Completion

2024-05-28

Publications

• Background 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.
• Background Koumenis C. ER stress, hypoxia tolerance and tumor progression. Curr Mol Med. 2006 Feb;6(1):55-69. doi: 10.2174/156652406775574604.
• Background Toulany 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 Gupta 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 Keys 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 Rose 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 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.
• Background Choe 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 Kim 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 Dent 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 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.
• Background 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.
• 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.

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Indications