AzTrials
AzTrials

Anal Cancer Stage III APhase 1CORINTHNCT04046133

Phase 1b/II Trial of Pembrolizumab Plus IMRT in Stage III/IV Carcinoma of Anus

A Phase 1 study testing Pembrolizumab in people with Anal Cancer Stage III A and Anal Cancer Stage III B, run by Cardiff University at 11 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The CORINTH trial is for patients with more advanced (stage 3 and 4) anal cancer. The numbers of patients with anal cancer is increasing and only 65% patients with this later stage anal cancer have not had a recurrence 3 years after treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
11 sitesin 2 countries
Study dates
19 Oct 2020to 30 Nov 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible for participation in this trial, the subject must:
  • Be willing and able to provide written informed consent/assent for the trial.
  • Age 18 years or over on day of signing informed consent.
  • Histologically proven Squamous Cell Cancer of Anus (SCCA) T3 / 4 N0 M0 or any N+ M0 or highly suspicious and confirmed by the MDT
  • Be willing to provide tissue sample either archival or repeat biopsy to be tested for HPV and p16.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
Show all 14Show fewer
  • Demonstrate adequate organ function performed within 10 days of treatment initiation:
  • Hematological: Absolute neutrophil count (ANC) ≥1.5 x 109/L, Platelets ≥100 x 109/L,
  • 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).
  • 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
  • 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.
  • 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  • 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

Who cannot join

  • The subject must be excluded from participating in the trial if the subject:
  • Has malignant tumour of non-epithelial origin (sarcoma)
  • Has any metastatic disease
  • Is unsuitable for radical CRT for whatever reason
  • 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.
  • Has a diagnosis of immunodeficiency (see 18. For patients with HIV who may be eligible) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Show all 23Show fewer
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 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 prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or previous VIN (vulval intra-epithelial neoplasia) or vulval cancer adequately treated, or previous adequately treated breast cancer / DCIS > 5 years ago.
  • 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.
  • Has known history of, or any evidence of 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 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 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.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected). Testing only required if patient has a history of either of these.
  • Has received a live vaccine within 30 days of planned start of study therapy. (Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.)

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United Kingdom10 sites

  • Aberdeen Royal Informary

    Aberdeen, Scotland, AB25 2ZN

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge

  • Velindre Cancer Centre

    Cardiff

  • East Suffolk and North Essex NHS Foundation Trust

    Colchester

  • The Leeds Teaching Hospitals NHS Trust

    Leeds

  • The Christie NHS Foundation Trust

    Manchester

  • Mount Vernon Cancer Centre

    Northwood, HA6 2RN

  • Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield

  • Swansea Bay University Local Health Board

    Swansea

Other trials in United Kingdom

Norway1 site

  • Oslo University Hospital

    Oslo, NO-0424

Other trials in Norway

About this study

Official title: Phase 1b/II Trial of Checkpoint Inhibitor (Pembrolizumab an Anti PD-1 Antibody) Plus Standard IMRT in HPV Induced Stage III/IV Carcinoma of Anus

The CORINTH trial is for patients with more advanced (stage 3 and 4) anal cancer. The numbers of patients with anal cancer is increasing and only 65% patients with this later stage anal cancer have not had a recurrence 3 years after treatment. Anal cancer responds well to chemo-radiation (CRT) and this would be the treatment used for standard clinical care. The chemotherapy in CORINTH will be the same as standard of care (Mitomycin and 5FU or capecitabine) and the radiotherapy (RT) will be delivered using a technique where the dose intensity of RT can be modulated for different areas of the tumor (Intensity Modulated RT - IMRT). Translational samples (tissue blocks and blood) will be collected at baseline with further blood and tissue samples during and after treatment.

Pembrolizumab, a relatively 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 called Programmed Death -1 (PD-1). The CORINTH study aims to see whether pembrolizumab, can be added safely to standard CRT. We will explore how safe the combination is and how well tolerated it is for patients with stage 3 and 4 anal cancer. If it is tolerable more patients will be treated to see if there is a similar or better clinical response.

Read more

The trial is designed in 3 groups of patients. All patients will receive eight infusions of pembrolizumab at three weekly intervals. Each infusion lasts approximately 1 hour. The first group will not get pembrolizumab until they have already had 4 weeks of CRT (Day 29). As long as this is not found to cause too many extra side effects, the next group will have infusions at the beginning of the third week of CRT. The final group (cohort 3) will start their pembrolizumab with the first day of CRT i.e. Day 1.

Initially each group will have 6 patients. Provided each group of patients finds the treatment tolerable and it is safe, more patients will be recruited into the group that receives the pembrolizumab earliest during their CRT. This will add further credence to the safety and tolerability of the combination and may provide a signal of how effective this treatment might be in improving outcomes for patients with more advanced anal cancer.

Read the detailed description

CORINTH is a multi center trial with a single arm. Patients will be recruited into 3 successive cohorts followed by an expansion of the final cohort. For each cohort the first dose of Pembrolizumab will be given at an earlier time point during the chemo-radiation (CRT).

Pembrolizumab will be given as an IV infusion every 21 days, and a total of 8 infusions per patient at 200mg per infusion. The first dose of pembrolizumab will be given at the following times:

COHORT 1: beginning at Week 5 day 1 of CRT schedule COHORT 2: beginning at Week 3 day 1 of CRT schedule COHORT 3: beginning at Week 1 day 1 of CRT schedule** Cohort 2 will be dependent on a Safety Review Committee (SRC) recommendation. If the SRC are concerned about toxicity in Cohort 1 but not sufficiently to stop the study, they are able to recommend that Cohort 2 can change to commence pembrolizumab at week 4. If the SRC are concerned about toxicity in Cohort 2 but not sufficiently to stop the study, they are able to recommend that Cohort 3 can change to commence pembrolizumab at week 2.

Potential participants will be under the care of a consultant who specializes in the treatment of anal cancer and the patient will have been identified as requiring CRT treatment for their anal cancer. They will be assessed for eligibility before being consented and allocated to the current cohort. # Patients will be monitored for Adverse Events which will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Treatment guidelines are given for any immune related or infusion related events. Adverse Event review will take place weekly during CRT and at every pembrolizumab visit as well as key time during follow up.

Patient reported outcomes will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) tool during CRT, pembrolizumab treatment and follow up. Patients will be followed up for 12 months.

Being tested
Pembrolizumab
Medical subject headings
Anus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Radiotherapy, Chemotherapy (Mytomycin or Mitomycin and Capecitabine)

    Pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer.

Study groups in NCT04046133
Study groupRoleWhat they receive
pembrolizumabExperimentalPatients with locally advanced (stage IIIA/B, T3/T4, any N, M0) anal cancer will receive pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT.
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability- 30 days post CRT

    To assess safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T 3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE - v.4.03) will be reported at 30 days post chemoradiotherapy.

    Measured: 30 days post chemoradiotherapy

  2. Safety and tolerability- 6 weeks post CRT

    To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 6 weeks post chemoradiotherapy.

    Measured: 6 weeks post chemoradiotherapy

  3. Safety and tolerability - 12 weeks post CRT

    To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 12 weeks post chemoradiotherapy.

    Measured: 12 weeks post chemoradiotherapy

  4. Safety and tolerability - 6 months post CRT

    To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 6 months post chemoradiotherapy.

    Measured: 6 months post chemoradiotherapy

  5. Safety and tolerability- 9 months post CRT

    To assess the safety and of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE Adverse Events v.4.03) will be reported at 9 months post chemo-radiotherapy.

    Measured: 9 months post chemoradiotherapy

  6. Safety and tolerability- 12 months post CRT

    To assess the safety of different schedules of exposure to pembrolizumab, an immune checkpoint inhibitor, concomitantly with standard CRT in patients with locally advanced T3/4 anal cancer. Grade 3 to 5 treatment related adverse events (CTCAE v.4.03) will be reported at 12 months post chemoradiotherapy.

    Measured: 12 months post chemoradiotherapy

Secondary outcomes (12)

  1. Adherence to protocol treatment

    Adherence to protocol treatment will be 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.

    Measured: Up to 6 months post chemoradiotherapy

  2. Recruitment

    Recruitment rate will be 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.

    Measured: 2 years

  3. Retention

    Retention will be 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.

    Measured: Up to 12 months post chemoradiotherapy

  4. Study eligibility

    Study eligibility will be assessed by the number of patients eligible and ineligible at screening and reasons for ineligibility.

    Measured: 2 years

  5. Clinical response assessment - 3 months post CRT

    Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 3 months post chemoradiotherapy.

    Measured: 3 months post chemoradiotherapy

  6. Clinical response assessment - 6 months post CRT

    Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 6 months post chemoradiotherapy.

    Measured: 6 months post chemoradiotherapy

  7. Clinical response assessment - 12 months follow up

    Clinical response assessment will be measured by RECIST v 1.1 (MRI) for the overall response rate (ORR) at 12 months follow up

    Measured: 12 months follow up

  8. Imaging response - 3 months post CRT

    Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 3 months post chemoradiotherapy.

    Measured: 3 months post chemo-radiotherapy

  9. Imaging response - 6 months post CRT

    Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 6 months post chemoradiotherapy.

    Measured: 6 months post chemoradiotherapy

  10. Imaging response - 12 months follow up

    Imaging response will be assessed by Tumor Regression Grade MRI by changes in Apparent Diffusion Coefficient (ADC) on DW sequences. Immune related modified RECIST assessments (MRI) at 12 months follow up.

    Measured: 12 months follow up

  11. Patient reported outcome - up to 6 months post CRT

    Patient-reported outcomes (PRO) will be measured by using the EORTC quality of life questionnaires during CRT and 6 months post-CRT.

    Measured: Up to 6 months post chemoradiotherapy

  12. Patient reported outcome - 12 months follow up

    Patient-reported outcomes (PRO) will be measured by using the EORTC quality of life questionnaires at 12 months follow up

    Measured: 12 months follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2019
  2. Study start19 Oct 2020
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion30 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04046133
Sponsor's protocol ID
SPON 1529-16
Acronym
CORINTH
Status last verified
Jul 2025
First submitted
29 Jan 2018
Last updated
5 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab in people with Anal Cancer Stage III A and Anal Cancer Stage III B, run by Cardiff University at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability- 30 days post CRT (time frame: 30 days post chemoradiotherapy). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04046133.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in