Trial of Pembrolizumab and Radiotherapy in Melanoma

NCT02562625 | Terminated Phase 2 Results DMC

• 1 other identifier: CCR 4251
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Around 13,000 participants are diagnosed with melanoma in the UK each year and that number is growing quicker than any other cancer. About 20% of participants will see their cancer return following their initial treatment and at present would survive a median time of 912 months. In recent years, the development of new effective drugs has revolutionised the treatment of advanced melanoma, However, response rates are still low and new therapeutic approaches are needed. This is a phase II study to look at the effectiveness and safety of the combination of a new drug called pembrolizumab plus radiotherapy compared to pembrolizumab alone. The purpose of this study is to see if the addition of radiotherapy to pembrolizumab is better than pembrolizumab alone by measuring how long these treatments can control the growth of the cancer. Also it will assess if by adding radiotherapy the investigators can see its effects not only in the tumour that has had radiotherapy but also in other tumours in the rest of the body.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective: To Evaluate if Radiotherapy Will Enhance the Efficacy of Pembrolizumab in the Treatment of Patients With Metastatic Melanoma by Induction of an Abscopal Effect.

  Percentage of patients with improved tumour response rate (CR/PR) according to the RECIST v1.1 criteria at 12 weeks post treatment start date with the combination therapy of pembrolizumab plus radiotherapy.

  From date of randomisation until week 12 from start of treatment

Other Outcomes (6)

• Evaluating Response Rates by RECIST v1.1 Post Treatment

  RECIST tumour assessments completed at screening and every 12 weeks after 1st dose of pembrolizumab or during additional imaging time points and at early termination of treatment until date of first documented progression or end of trial (36 months).

• Exploratory Objective: Identifying Biomarkers That Correlate With Immunological Response to Therapy

  From date of randomisation until the date of first documented progression or date of death from any cause, whichever comes first.

• Evaluating Response in Non-irradiated Lesions

  From date of randomisation until the date of first documented progression or date of death from any cause, whichever comes first.

Study Arms (2)

Pembrolizumab Alone

EXPERIMENTAL

If the patient is randomised to the Pembrolizumab Arm Only then they will receive 200mg of pembrolizumab every 3 weeks.

Drug: Pembrolizumab

Pembrolizumab plus Radiotherapy

EXPERIMENTAL

If The patient is randomised to this arm they will receive 200mg of pembrolizumab every 3 weeks in combination with a radiotherapy dosage of 24Gy in 3 fractions to be given over 3 consecutive days (only).

Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

Pembrolizumab DRUG

Powder solution for infusion

Pembrolizumab Alone; Pembrolizumab plus Radiotherapy

Radiotherapy RADIATION

24Gy

Pembrolizumab plus Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• Have a diagnosis of stage III (unresectable) or stage IV cutaneous melanoma or melanoma of unknown primary, as per AJCC staging system
• Informed metastatic disease by diagnostic biopsy
• Be more than 18 years of age on day of signing informed consent
• Have at least one lesion and a maximum of 3 which are appropriate targets for high dose radiotherapy. This lesion must be 1cm-5cm in size and measurable by RECIST v1.1
• Have in addition at least one other lesion which will not be irradiated but must be measurable by RECIST v1.1 to assess the abscopal effect of the treatment
• Have a performance status of 0 or 1 on the ECOG performance scale
• Demonstrate adequate organ function as defined in table 1 below. All screening labs should be performed within 7 days of randomisation
• Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to randomisation. 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
• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

You may not qualify if:

• Has lesions that if irradiated would result in unacceptable radiation induced toxicity to normal tissue, in particular to the CNS and bowel
• Requires palliative radiotherapy for symptom control
• Is currently participating in or has participated in a study of an investigational agent or device within 4 weeks of the first dose of trial 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 monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e. ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: patients with an AE ≤Grade 2 neuropathy are an exception to this criterion and may qualify for the study
• 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 history of severe colitis related to previous immunotherapy treatment
• 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 known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• 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.
• Has evidence of interstitial lung disease or active, non-infectious 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

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• University of Manchester: collaborator
• University of Leeds: collaborator

Study Sites (1)

Royal Marsden

London, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

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

perm.trial@rmh.nhs.uk

(+44) 02089156666

Study Officials

• James Larkin, MD

  Royal Marsden NHS Foundation Trust

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2015
• First Posted: September 29, 2015
• Study Start: August 11, 2016
• Primary Completion: March 1, 2020
• Study Completion: October 1, 2021
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Locations

GB (1)