Locally advanced (stage IIIA/B, T3/T4, any N,M0) anal cancer MedDRA version: 20.0 Level: PT Classification code 10061424 Term: Anal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible for participation in this trial, the subject must: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Age 18 years or over on day of signing informed consent. 3. Histologically proven Squamous Cell Cancer of Anus (SCCA) Stage IIIA/B (T3/4, +/- any N, M0) anal cancer or highly suspicious and confirmed by the MDT 4. Be willing to provide tissue sample either archival or repeat biopsy to be tested for HPV and p16. 5. Have a performance status of 0 or 1 on the ECOG Performance Scale. 6. Demonstrate adequate organ function performed within 10 days of treatment initiation. a. Haematological: Absolute neutrophil count (ANC) =1.5 x 109/L, Platelets =100 x 109/L, Haemoglobin =9 g/dL or =5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) b. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN (unless subject 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 subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants). c. 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 subject with creatinine levels > 1.5 X institutional ULN d. Hepatic Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for subjects with total bilirubin levels > 1.5 ULN 7. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 15.9 – Contraception and pregnancy, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 9. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 15.9- Contraception and pregnancy, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: The subject must be excluded from participating in the trial if the subject: 1. Has malignant tumour of non-epithelial origin (sarcoma) 2. Has any metastatic disease 3. Is unsuitable for radical CRT for whatever reason 4. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 5. 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. Patients on long-term physiological doses of steroid (¬ 5 years ago. 11. 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 (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 12. Has known history of, or any evidence of active, non-infectious pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. 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. 17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) 19. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pembrolizumab, a new drug, is a monoclonal antibody that enhances the body’s immune response to cancer cells by acting on a receptor on the surface of T-cells. This receptor is called Programmed Death-1 (PD-1). The CORINTH study aims to see whether this new drug, pembrolizumab, can be added safely to standard chemoradiotherapy. We will explore how safe the combination is and how well tolerated it is for patients with stage T3/4 anal cancer.;Secondary Objective: 1.-Assess the feasibility of combining pembrolizumab with standard chemoradiotherapy (CRT) in patients eligible for the trial, in a series of sequential cohorts (n=6) where in each cohort pembrolizumab will be introduced earlier in the patient’s CRT. -Evaluate study eligibility, recruitment, planned treatment in terms of adherence to protocol and treatment retention in each cohort. 2. Evaluate CRR of the different schedules of exposure of pembrolizumab in CRT in patients included, and assess if the addition of pembrolizumab offers at least a similar clinical CR as that of SoC (at 3, 6 months post CRT and at 12 months FU). 3. assess tumour regression with MRI evaluation at 3 & 6 months post CRT and at 12 months FU. 4. assess PROs as reported by the patients during the CRT through pembrolizumab treatment, at 6 months post completion of CRT and at 12 months FU to compare outcomes in three sequential cohorts receiving pembrolizumab at different timepoints of their CRT.;Primary end point(s): Safety and tolerability of a combination of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer by assessing AEs / SAEs and extent of protocol adherence by study population.;Timepoint(s) of evaluation of this end point: Mandatory safety visit at 30 days post chemo-radiotherapy Early toxicity check 6 weeks post chemo-radiotherapy Later toxicity check at 12 weeks post chemo-radiotherapy Late toxicity | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Feasibility of combining pembrolizumab, an immune checkpoint inhibitor, with standard CRT at different schedules in patients with locally advanced T3/4 anal cancer as measured by: a.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. b.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. c.Recruitment rate as assessed by the number of days study 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. d.Study eligibility as assessed by the number of patients eligible and ineligible at screening and reasons for ineligibility. 2.Clinical response assessment as measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 3 and 6 months post-CRT and 12 months follow up. 3.Patient-reported outcomes (PRO) using the PRO-CTCAE tool during CRT, pembrolizumab monotherapy and 6 post CRT and 12 months follow-up to assess symptomatic toxicity both acute and late.;Timepoint(s) of evaluation of this end point: A statistical analysis plan will be developed before the earliest toxicity check 30 days post CRT. No interim analysis is planned for this study. Efficacy Analysis: Clinical response assessment as measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 3 months and 6 months post-CRT and at 12 months follow up. Patient Reported Outcomes Analysis: Patient reported outcomes will be measured by the PRO-CTCAE tool during CRT, pembrolizumab monotherapy and 6 and 12 months follow-up. | — |
Countries
Norway, United Kingdom
Contacts
Public ContactMartina Svobodova
Centre for trials research
Outcome results
None listed