Clinical Trials /

Neo-adjuvant Pembrolizumab and Radiotherapy in Localised MSS Rectal Cancer

NCT04109755

Description:

This project investigates the clinical and biological impact of combining immunotherapy (pembrolizumab) with short course radiotherapy (5Gy, five times) in the neo-adjuvant treatment of localised microsatellite stable (MSS) rectal cancer.

Related Conditions:
  • Rectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neo-adjuvant Pembrolizumab and Radiotherapy in Localised MSS Rectal Cancer
  • Official Title: A Phase II Study to Evaluate Safety and Efficacy of Neo-adjuvant Pembrolizumab and Radiotherapy in Localised MSS Rectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: PEMREC
  • NCT ID: NCT04109755

Conditions

  • Rectum Cancer
  • Rectal Cancer

Interventions

DrugSynonymsArms
PembrolizumabExperimental

Purpose

This project investigates the clinical and biological impact of combining immunotherapy (pembrolizumab) with short course radiotherapy (5Gy, five times) in the neo-adjuvant treatment of localised microsatellite stable (MSS) rectal cancer.

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalShort Course Radiation Therapy (5 x 5 Gy in 1 week, SCRT) with 4 injections of Pembrolizumab starting on the first day of radiotherapy and surgery
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male/female participants who are at least 18 years of age on the day of signing
             informed consent with histologically confirmed diagnosis of rectal adenocarcinoma will
             be enrolled in this study.

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.

          -  Patients with previously untreated localized T3-T4 N0 or T any or N1-2, M0 rectal
             adenocarcinoma.

          -  Tumour must be microsatellite stable (MSS).

          -  A multi-disciplinary tumour board should recommend neo-adjuvant short course
             radiotherapy and surgery.

          -  Have provided archival tumour tissue sample or newly obtained core or excisional
             biopsy of a tumour lesion not previously irradiated. Formalin-fixed paraffin embedded
             (FFPE) tissue blocks are preferred.

          -  Have adequate organ function as defined in the following table. Specimens must be
             collected within 10 days prior to the start of study treatment.

        Exclusion Criteria:

          -  Has a microsatellite instable tumour (MSI-High).

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
             OX 40, CD137).

          -  Has received for the same disease prior systemic anti-cancer therapy including
             investigational agents prior to starting pembrolizumab. Note: If participant received
             major surgery, they must have recovered adequately from the toxicity and/or
             complications from the intervention prior to starting study treatment.

          -  Has received prior radiotherapy for the same disease. If treated with radiotherapy for
             another disease, participants must have recovered from all radiation-related
             toxicities, not require corticosteroids, and not have had radiation pneumonitis.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment. Note: Participants who have entered the follow-up phase of an
             investigational study may participate as long as it has been 4 weeks after the last
             dose of the previous investigational agent.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
             cervical cancer in situ) that have undergone potentially curative therapy are not
             excluded.

          -  Has known active CNS metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study treatment.

          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a known history of Human Immunodeficiency Virus (HIV).

          -  Has a known history of Hepatitis B virus (defined as Hepatitis B surface antigen
             [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA > 1.5E1 is
             detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
             unless mandated by local health authority.

          -  Has a known history of active TB (Bacillus Tuberculosis).

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumour regression grade
Time Frame:12 weeks after start
Safety Issue:
Description:To assess the tumour regression grade (TRG) after short course radiotherapy when given together with pembrolizumab, using the Mandard regression grade score

Secondary Outcome Measures

Measure:Tolerability and safety
Time Frame:5 years
Safety Issue:
Description:To assess tolerability and safety of pembrolizumab given with short course radiotherapy before surgery, using the common terminology criteria for adverse events (CTCAE) Version 4.0
Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:To estimate overall survival (OS), defined as the time between the date of the study entry and the date of death due to any cause. Subjects who have not died at the time of last known follow-up will be censored.
Measure:Disease-free survival
Time Frame:3 years
Safety Issue:
Description:To estimate disease-free survival (DFS), defined as the time between the date of the study entry and the date of recurrence, second primary cancer, or death without evidence of recurrence or second primary cancer.
Measure:Locoregional relapse-free survival
Time Frame:5 years
Safety Issue:
Description:To estimate locoregional relapse-free survival (LRRFS), defined as the time between the date of the surgery and local or regional recurrence. LRRFS is evaluated in patients who had an R0 resection only
Measure:Distant metastasis-free survival
Time Frame:5 years
Safety Issue:
Description:To estimate distant metastasis-free survival (DMFS), defined as the time between the date of the surgery and metastatic recurrence.
Measure:Quality of life
Time Frame:5 years
Safety Issue:
Description:EORTC QLQ-C30 and EORTC QLQ-CR29

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Hospital, Geneva

Trial Keywords

  • Rectal cancer
  • Immunotherapy
  • Short course radiotherapy
  • 5x5Gy
  • Pembrolizumab
  • Localised rectal cancer

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