The CORINTH Trial: Study of Checkpoint Inhibitor Pembrolizumab plus standard chemoradiation in anal cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cardiff University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-01-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

MSD

External identifiers

EU CT number

2024-515369-33-00

EudraCT number

2017-002300-27

ClinicalTrials.gov

NCT04046133

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy

To assess the safety and tolerability of two different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer

Secondary objectives 4

1. To assess the feasibility of two different schedules of exposure to pembrolizumab concomitantly with standard CRT with locally advanced anal cancer in terms of adherence to trial eligibility, recruitment, planned treatment, and retention
2. To evaluate the response rates of two different schedules of exposure to pembrolizumab with standard CRT in patients with locally advanced anal cancer, to ensure that they offer at least a similar clinical complete response (cCR) rate
3. To evaluate Tumour Regression Grade (TRG) MRI including Diffusion Weighted Imaging (DWI) sequences (b value 0-1000) where possible to assess changes in Apparent Diffusion Coefficient (ADC). Immune related modified RECIST assessments (MRI) at 3 and 6 months post-CRT and at 12 months follow up
4. To evaluate any additional detrimental effects on patient-reported outcomes (PRO) from the two different schedules of exposure to pembrolizumab with standard CRT in patients with locally advanced anal cancer, by using the EORTC tool during CRT through pembrolizumab monotherapy to 12 months follow-up.

Conditions and MedDRA coding

Anal cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Be willing and able to provide written informed consent
2. Age 18 years or over on day of signing informed consent
3. Histologically proven Squamous Cell Cancer of Anus (SCCA) T3 / 4 N0 M0 or any N+ M0 or highly suspicious and confirmed by the MDT
4. Have a performance status of 0 or 1 on the ECOG Performance Scale
5. Demonstrate adequate organ function performed within 10 days of treatment initiation
6. 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)
7. 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.
8. 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.
9. 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 20

1. Has malignant tumour of non-epithelial origin (i.e. sarcoma)
2. Has any metastatic disease
3. Unsuitable for radical CRT for whatever reason
4. 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.
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.
6. Has a known history of active TB (Bacillus Tuberculosis).
7. Hypersensitivity to pembrolizumab or any of its excipients
8. 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
9. 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
10. Has a known additional malignancy that is progressing or requires active treatment.
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).
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 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.
15. Has known psychiatric or substance abuse disorders that would make cooperation with the requirements of the trial challenging.
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).
20. Has received a live vaccine within 30 days of planned start of trial therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 7

1. 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.
2. 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.
3. 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.
4. Trial eligibility as assessed by the number of patients eligible and ineligible at screening and reasons for ineligibility.
5. 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.
6. 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.
7. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cardiff University

Sponsor organisation

Cardiff University

Address

Neuadd Meirionnydd, Heath Park Way, Heath Heath Park Way Heath

City

Cardiff

Postcode

CF14 4YU

Country

United Kingdom

Scientific contact point

Organisation

Cardiff University

Contact name

Margherita Carucci

Public contact point

Organisation

Cardiff University

Contact name

Margherita Carucci

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications