NCT03144466: PAPAYA

A Study of Pembrolizumab And Platinum With Radiotherapy in Cervix Cancer

Terminated Phase 1 Last updated 12 June 2019

What this trial tests

Phase 1 trial testing Pembrolizumab in Cervix Cancer in 1 participant. Terminated before completion.

Timeline

21 December 2017

Primary endpoint
31 January 2019

31 January 2019

Quick facts

Lead sponsor	Royal Marsden NHS Foundation Trust
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	1
Start date	21 December 2017
Primary completion	31 January 2019
Estimated completion	31 January 2019
Sites	1 location across United Kingdom

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Cervix Cancer — all drugs for Cervix Cancer →

Sponsor

Royal Marsden NHS Foundation Trust

Who can join

18 and older, female only, with Cervix Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Locally advanced cervix cancers (stage 1B-IV) are usually treated with radiotherapy, concomitant cisplatin chemotherapy and brachytherapy. Failure to achieve locoregional control (LRC) remains a problem, especially in the setting of stage III/IV disease. More importantly, however, the dominant unresolved problem remains the occurrence of distant metastatic relapse. With the knowledge that 99% of all cervix cancer is associated with human papillomavirus (HPV) infection, there is a strong rationale to consider immunomodulatory strategies in the radical management of this disease. Therefore, in this research protocol the investigator will treat patients with stage 1B-IVA carcinoma of the cervix planned to receive radical radiotherapy with concomitant cisplatin and brachytherapy. The research involves adding a new therapy in the form of an antiPD1 monoclonal antibody (pembrolizumab) to the standard treatment of radiotherapy combined with cisplatin chemotherapy and brachytherapy. This treatment seeks to activate the patient's own immune system to attack the cancer cells - and the investigator believes that adding this treatment during standard treatment may be particularly effective. Patients will receive an initial dose of pembrolizumab 2 weeks before starting a course of chemoradiotherapy and brachytherapy. In the first instance, patients will receive 100 mg of pembrolizumab and, if this is safe and tolerable in the first 3 patients, the dose will be increased to 200 mg for all other patients. Radiation will be delivered on 28 occasions with chemotherapy given intravenously in weeks 0, 1, 2 and 3. Brachytherapy will be given on 3 occasions after completion of the radiation. Additional doses of pembrolizumab will be given every 3 weeks for a further 7 doses. The investigator will assess the feasibility and safety of the combination of pembrolizumab with radiotherapy and cisplatin.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
   Vafaei S, Zekiy AO, Khanamir RA, Zaman BA, et al · · 2022 · cited 190× · PMID 34980128 · DOI 10.1186/s12935-021-02407-8
2. PD-1/PD-L1 Inhibitors in Cervical Cancer.
   Liu Y, Wu L, Tong R, Yang F, et al · · 2019 · cited 113× · PMID 30774597 · DOI 10.3389/fphar.2019.00065
3. The current status of immunotherapy for cervical cancer.
   Orbegoso C, Murali K, Banerjee S. · · 2018 · cited 47× · PMID 30534022 · DOI 10.1016/j.rpor.2018.05.001
4. Combination Immune Checkpoint Blockade Strategies to Maximize Immune Response in Gynecological Cancers.
   Liu YL, Zamarin D. · · 2018 · cited 39× · PMID 30421009 · DOI 10.1007/s11912-018-0740-8
5. Current Possibilities of Gynecologic Cancer Treatment with the Use of Immune Checkpoint Inhibitors.
   Grywalska E, Sobstyl M, Putowski L, Roliński J. · · 2019 · cited 35× · PMID 31547532 · DOI 10.3390/ijms20194705
6. Keynote-158 study, FDA granted accelerated approval of pembrolizumab for the treatment of patients with advanced PD-L1-positive cervical cancer.
   Borcoman E, Le Tourneau C. · · 2020 · cited 34× · PMID 33437810 · DOI 10.21037/atm-20-2656
7. Immunotherapy for Uterine Cervical Cancer.
   Kagabu M, Nagasawa T, Fukagawa D, Tomabechi H, et al · · 2019 · cited 29× · PMID 31533297 · DOI 10.3390/healthcare7030108
8. Immune checkpoint inhibitors in cervical cancer: Current status and research progress.
   Xie Y, Kong W, Zhao X, Zhang H, et al · · 2022 · cited 28× · PMID 36387196 · DOI 10.3389/fonc.2022.984896