Pembrolizumab for Anal cancer | Squamous cell carcinoma of anus

Inclusion criteria

• {"criterion_text":"- Be willing and able to provide written informed consent\n- Age 18 years or over on day of signing informed consent\n- Histologically proven Squamous Cell Cancer of Anus (SCCA) T3 / 4 N0 M0 or any N+ M0 or highly suspicious and confirmed by the MDT\n- Have a performance status of 0 or 1 on the ECOG Performance Scale\n- Demonstrate adequate organ function performed within 10 days of treatment initiation\n- Haematological: Absolute neutrophil count (ANC) ≥1.5 x 109/L, Platelets ≥100 x 109/L, Haemoglobin ≥9 g/dL or ≥5.6 Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants), Activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants). Renal: Serum creatinine ≤1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for patient with creatinine levels > 1.5 x institutional ULN Hepatic Serum total bilirubin ≤ 1.5 x ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN mmol/L without transfusion or EPO dependency (within 7 days of assessment)\n- Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n- Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the trial through 120 days after the last dose of trial medication.\n- Male patients must agree to use an adequate method of contraception starting with the first dose of trial therapy through 120 days after the last dose of trial therapy"}

Exclusion criteria

• {"criterion_text":"- Has malignant tumour of non-epithelial origin (i.e. sarcoma)\n- Has a known additional malignancy that is progressing or requires active treatment.\n- 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).\n- Has known history of, or any evidence of active, non-infectious pneumonitis.\n- Has an active infection requiring systemic therapy.\n- 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.\n- Has known psychiatric or substance abuse disorders that would make cooperation with the requirements of the trial challenging.\n- Is pregnant or breastfeeding or expecting to conceive or father 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.\n- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.\n- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)\n- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected).\n- Has any metastatic disease\n- Has received a live vaccine within 30 days of planned start of trial therapy.\n- Unsuitable for radical CRT for whatever reason\n- Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 4 weeks of the first dose of treatment.\n- 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.\n- Has a known history of active TB (Bacillus Tuberculosis).\n- Hypersensitivity to pembrolizumab or any of its excipients\n- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to trial Day 1 or who has not recovered (i.e., ≤ Grade 1 at baseline) from adverse events due to agents administered more than 4 weeks earlier\n- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to trial Day 1 or who has not recovered (i.e., ≤ Grade 1 at baseline) from adverse events due to a previously administered agent"}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability of a combination of two different schedules of exposure to pembrolizumab concomitantly with standard CRT in patients with locally advanced anal cancer by assessing AEs / SAEs and extent of protocol adherence by trial population","definition_or_measurement_approach":"Assessment of AEs / SAEs and extent of protocol adherence by trial population (i.e., monitoring adverse events/serious adverse events and protocol adherence measures)."}

Secondary endpoints

• {"endpoint_text":"- Feasibility of combining pembrolizumab with standard CRT in two different schedules in patients with locally advanced anal cancer as measured by: Adherence to protocol treatment, as assessed by numbers of patients receiving per protocol treatment, dose delays, treatment reductions, treatment discontinuation and documenting the reasons for delays or discontinuation for each patient.","definition_or_measurement_approach":"Measured by numbers of patients receiving per-protocol treatment, dose delays, treatment reductions, treatment discontinuations and reasons for delays/discontinuations."}
• {"endpoint_text":"- Retention as assessed by the proportion of patients withdrawing from protocol treatment and number of patients lost to follow-up with documentation of reasons in each case.","definition_or_measurement_approach":"Proportion of patients withdrawing from treatment and number lost to follow-up with documentation of reasons."}
• {"endpoint_text":"- Recruitment rate as assessed by the number of days trial is open for recruitment, the number of patients screened, the number of screened patients not recruited and why and the number (proportion) of patients recruited.","definition_or_measurement_approach":"Assessment of recruitment duration (days open), number screened, screen failures with reasons, and number/proportion recruited."}
• {"endpoint_text":"- Trial eligibility as assessed by the number of patients eligible and ineligible at screening and reasons for ineligibility.","definition_or_measurement_approach":"Counts of eligible vs ineligible at screening with reasons for ineligibility."}
• {"endpoint_text":"- Clinical response assessment for the overall response rate (ORR) at 12 weeks post-CRT and at 6 months post-CRT and 12 months follow up.","definition_or_measurement_approach":"Overall response rate (ORR) assessed at 12 weeks post-CRT, 6 months post-CRT and at 12 months follow-up."}
• {"endpoint_text":"- Imaging response assessments by TRG MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 3 and 6 months post-CRT and at 12 months follow up.","definition_or_measurement_approach":"Tumour Regression Grade (TRG) MRI including DWI sequences with ADC changes; immune-related modified RECIST on MRI at 3 and 6 months post-CRT and at 12 months follow-up."}
• {"endpoint_text":"- Patient-reported outcomes (PRO) using the EORTC tool during CRT, pembrolizumab monotherapy and 6 months post-CRT and 12 months follow-up to assess symptomatic toxicity both acute and late.","definition_or_measurement_approach":"PROs collected using EORTC tool during CRT, during pembrolizumab monotherapy, at 6 months post-CRT and at 12 months follow-up to assess acute and late symptomatic toxicity."}

Norway

Earliest CTIS Part Ii Submission Date

11-12-2024

Latest Decision Or Authorization Date

14-01-2025

Processing Time Days

34

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Cardiff University

Organisation Type

Educational Institution

Country Of Registered Address

United Kingdom

Third parties

• {"country":"","full_name":"MSD","duties_or_roles":"Monetary support","organisation_type":""}