A Study of Pembrolizumab And Platinum With Radiotherapy in Cervix Cancer

NCT03144466 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: CCR 4268
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cervix Cancer

Outcome Measures

Primary Outcomes (1)

• Number and Percentage of Patients With Dose Limiting Toxicities.

  To establish the maximum tolerated dose (MTD) of pembrolizumab that can be safely combined with radiotherapy, brachytherapy and cisplatin in the absence of dose limiting toxicities (DLTs)

  Time from Treatment commencement date until 12 weeks following end of radiation treatment, up to 18 weeks

Secondary Outcomes (5)

• Evaluate Toxicities of Treatment

  Treatment commencement through study completion, up to 19 weeks after last dose of Pembrolizumab

• Response Rates

  Assessments at week 5 and week 12 following end of radiation treatment

• Overall Survival (OS)

  Time from treatment commencement date until 1 and 2 years assessments.

• Late Radiotherapy Toxicity

  Assessment at 12 weeks following end of radiation therapy.

• Progression Free Survival (PFS)

  Time from treatment commencement date until 1 and 2 years assessments.

Study Arms (3)

Part A - Starting dose

EXPERIMENTAL

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).

Combination Product: Pembrolizumab

Part A - Escalation dose

EXPERIMENTAL

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).

Combination Product: Pembrolizumab

Part B - Expansion phase

EXPERIMENTAL

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.

Combination Product: Pembrolizumab

Interventions

Pembrolizumab COMBINATION_PRODUCT

antiPD1 monoclonal antibody

Also known as: KEYTRUDA

Part A - Escalation dose; Part A - Starting dose; Part B - Expansion phase

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed FIGO stage 1B - IVA carcinoma of the cervix planned to receive radical radiotherapy with concomitant cisplatin and brachytherapy. Pelvic lymph node but not para-aortic lymph node involvement is permitted.
• ECOG PS 0-1
• Be willing and able to provide written informed consent for the trial.
• Be \>= 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Demonstrate adequate organ function (as defined in Table 1 of the trial protocol) all screening tests should be performed within 10 days prior to confirmation of study eligibility.
• Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• For Concomitant cisplatin GFR\>50ml/min, no contraindications to cisplatin (pre-existing tinnitus or neuropathy)

You may not qualify if:

• Requires para-aortic radiotherapy
• Has had previous pelvic radiotherapy
• Has had bowel resection, history of inflammatory bowel disease or autoimmune condition
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody, chemotherapy, targeted small molecule therapy, or radiation therapy. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

pembrolizumab

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

Results Point of Contact

• Title: PAPAYA Senior Trial Manager
• Organization: The Royal Marsden NHS Foundation Trust

papaya.trial@rmh.nhs.uk

(+44) 020 8915 6666

Study Officials

• Susan Lalondrelle

  Royal Marsden Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2017
• First Posted: May 8, 2017
• Study Start: December 18, 2017
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: May 20, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)