Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial

Supriya Chopra, Jayant Sastri Goda, Prachi Mittal, Jaahid Mulani, Sidharth Pant, Venkatesh Pai, Sadhna Kannan, Kedar Deodhar, Manjunath Nookala Krishnamurthy, Santosh Menon, Mayuri Charnalia, Sneha Shah, Venkatesh Rangarajan, Vikram Gota, Lavanya Naidu, Sheela Sawant, Praffula Thakkar, Palak Popat, Jaya Ghosh, Sushmita Rath, Seema Gulia, Reena Engineer, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Jayant Sastri Goda, Prachi Mittal, Jaahid Mulani, Sidharth Pant, Venkatesh Pai, Sadhna Kannan, Kedar Deodhar, Manjunath Nookala Krishnamurthy, Santosh Menon, Mayuri Charnalia, Sneha Shah, Venkatesh Rangarajan, Vikram Gota, Lavanya Naidu, Sheela Sawant, Praffula Thakkar, Palak Popat, Jaya Ghosh, Sushmita Rath, Seema Gulia, Reena Engineer, Umesh Mahantshetty, Sudeep Gupta

Abstract

Introduction: In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).

Methods and analysis: Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.

Ethics and dissemination: The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.

Trial registration number: The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Keywords: adult radiotherapy; chemotherapy; gynaecological oncology; radiation oncology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Figure depicting the workflow of the clinical trial. At baseline patients undergo (A) MRI of the pelvis and (B) positron emission tomography (PET) scan for clinical staging. Additional research biopsy is obtained for performing immunohistochemistry (C, D). Following this patients are started on allocated intervention. Panel E and F demonstrate the clinical treatment provided to the patients with radiation along with weekly concurrent cisplatin following which patients undergo image guided brachytherapy. Panel E and F depicts the brachytherapy procedure and imaging. P-Akt, phosphorylation of protein kinase B.RT, radiotherapy; PK, pharmacokinetic; BT, brachytherapy.

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