A Study of Pembrolizumab And Platinum With Radiotherapy in Cervix Cancer

Sponsor
Royal Marsden NHS Foundation Trust
Study ID
NCT03144466
Phase
PHASE1
Status
Terminated

Conditions

  • Cervix Cancer

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — COMBINATION_PRODUCT
    antiPD1 monoclonal antibody

Study Details

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.

Key Dates

Start date
Dec 18, 2017
Status verified
May 2026
Primary completion
Jan 31, 2019
Completion
Jan 31, 2019

Study Design

Enrollment
1 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Part A - Starting dose
    100mg of pembrolizumab in n=3 patients, administered in 8 cycles every 3 weeks for a total of 18 weeks commencing two weeks prior to first fraction of radiotherapy and given in combination with Radical Radiotherapy, Brachytherapy and Cisplatin Chemotherapy. Increase in cohort by three patients to n=6 patients provided no more than 1/3 patients experience a Dose Limiting Toxicity (DLT).
  • Experimental: Part A - Escalation dose
    Escalation of dose to 200mg of pembrolizumab in a further n=3 patients provided no more than 1/6 patients at starting dose experience a DLT. Increase in cohort by three patients to n=6 patients provided no more than 1/3 patients experience a Dose Limiting Toxicity (DLT).
  • Experimental: Part B - Expansion phase
    Recruitment of expansion cohort of n=14 patients using Maximum Tolerated Dose (MTD) of Pembrolizumab as determined in the dose escalation phase. MTD to be administered in 8 cycles every 3 weeks for a total of 18 weeks commencing two weeks prior to first fraction of radiotherapy and given in combination with Radical Radiotherapy, Brachytherapy and Cisplatin Chemotherapy.

Primary Outcome Measure

Number and Percentage of Patients With Dose Limiting Toxicities. [ Time Frame: Time from Treatment commencement date until 12 weeks following end of radiation treatment, up to 18 weeks ]

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