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Metastatic Colorectal CancerPhase 2NCT03867799

iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer

A Phase 2 study testing Nivolumab in people with Metastatic Colorectal Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited Kingdom
Study dates
27 Mar 2019to Sep 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Male or female patients aged ≥18 years
  • Patients with histologically confirmed advanced/metastatic RAS/RAF wild type colon or rectal adenocarcinoma who had a prior radiological response to EGFR blockade as a single agent or in combination with chemotherapy but have subsequently progressed/ become refractory to this treatment based on physician judgment. Patients should not have received any other systemic anti-cancer therapy between the end of treatment with EGFR inhibitors as a single agents or in combination with chemotherapy and screening for the iSCORE study
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Estimated life expectancy of at least 3 months at the time of informed consent per Investigator assessment
  • Adequate organ functioning as defined by the following:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (stable off any growth factor within 4 weeks prior to first study drug administration) ii. Platelet count ≥ 100 × 109/L (Transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) iii. Haemoglobin ≥ 8.5 g/dL (Transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) iv. Creatinine < 1.5 X ULN or creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula) v. AST and ALT levels ≤ 3 × ULN vi. Lipase and amylase < 1.5 ULN vii. Total bilirubin level ≤ 1.5 ULN (except patients with Gilbert's Syndrome who must have a normal direct bilirubin) viii. Normal thyroid function or on stable hormone supplementation per investigator assessment ix. Albumin >28 g/dL x. LVEF assessment with documented LVEF ≥ 50% by TTE within 6 months from first study drug administration
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  • Negative serum or urine pregnancy test at screening for women of childbearing potential**
  • Highly effective contraception for both male and female patients throughout the study and for at least 165 days for women 225 days for males after the last treatment administration if the risk of conception exists. Please refer to Section 9.15 - Pregnancy reporting for details of acceptable and unacceptable methods of contraception.
  • Patient must consent and be eligible to undergo mandatory baseline and sequential biopsies; in such case as a specimen cannot be obtained at acceptable clinical risk as judged by the Investigator then patients may still be included in the study. Patients must not be anti-coagulated at the time of biopsy or on aspirin/clopidogrel for 7 days pre-biopsy
  • Resolved acute effects of prior therapy to baseline severity or ≤Grade 1 except for AEs not constituting a safety risk by investigator judgement
  • Signed and dated informed consent
  • Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other procedures. Prisoners and patients who are involuntarily incarcerated are excluded
  • Presence of measurable disease as defined by RECIST v 1.1 criteria for response assessment ** Defined as a pre-menopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception

Who cannot join

  • Patients are not eligible for the trial if any of the exclusion criteria below are met:
  • Systemic therapy within 4 weeks prior to the planned administration of the first study treatment dose
  • Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 48 hours prior to study entry and there is at least one measurable lesion that has not been irradiated
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
  • Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs such as but not limited to anti-CTLA-4, anti-PD-1, anti-PDL1, anti-PD-2, anti-KIR, anti-CD137, anti-LAG-3, anti-OX40 antibodies or IDO or CXCR2 targeted agents
  • Known severe hypersensitivity reactions (Grade ≥ 3 NCI CTCAE v 5.0) to monoclonal antibodies or related compounds or any of their components (e.g. history of severe hypersensitivity reactions to drugs formulated with polysorbate 80), any history of anaphylaxis or uncontrolled asthma (defined a 3 or more features of partially controlled asthma)
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  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Active infection requiring systemic therapy
  • Any active malignancy, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or other locally curable cancers including superficial bladder cancer, carcinoma in situ of the prostate, cervix or breast
  • Significant acute or chronic infections including, among others:
  • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
  • All patients with brain metastases, except those meeting the following criteria:
  • Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
  • No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
  • Patients must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Any active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
  • Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
  • Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
  • Uncontrolled angina within the 3 months prior to consent
  • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation)
  • QTc prolongation > 480 msec
  • History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc )
  • Cardiovascular disease-related requirement for daily supplemental oxygen
  • History of two or more MIs OR two or more coronary revascularization procedures
  • Patients with history of myocarditis, regardless of aetiology
  • Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Patients with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤1 x ULN. If TnT or TnI levels are >1 to 2 × ULN within 24 hours, the patient may undergo a cardiac evaluation and be considered for treatment based on the discretion of the PI. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 x ULN, the patient may undergo a cardiac evaluation and be considered for treatment, based on the discretion of the CI
  • Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 5.0 Grade > 1) except alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
  • Pregnancy or lactation (females of childbearing potential must have a negative pregnancy test within 3 days prior to treatment initiation and every month during treatment
  • Known alcohol or drug abuse
  • Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Vaccination within 4 weeks of the first dose of study drugs and while on trial is prohibited except for administration of inactivated vaccines
  • A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: Immunotherapy Sequencing in COlon and REctal Cancer

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC.

Read the detailed description

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC.

Patients with metastatic RAS/RAF WT colorectal cancer who have previously had a radiological response to EGFR inhibitors i.e. Cetuximab or Panitumumab, either combined with chemotherapy or as single agents, but subsequently experienced progression of their disease will be eligible for the study. They will consent to the study ideally within 3 months having progressed/ become refractory to EGFR blockable and undergo a mandatory baseline biopsy within this time period.

Patients will receive Nivolumab and Relatlimab every 4 weeks and will start on study treatment as soon as possible after the baseline biopsy. After starting on the study drugs, there will be a mandatory 'on-treatment' biopsy at day 21 ± 3 days. Response assessments in the form of either CT or MRI scans will take place every 8 weeks throughout the study for the 12 months and every 12 weeks from 12 months onwards. Patients will continue on the study until progressive disease (PD) is confirmed by RECIST 1.1 or when maximum duration of treatment of 24 months has been reached

There will be the possibility of 'treating beyond progression' if participants are deriving clinical benefit from treatment to encompass the possibility of pseudoprogression. At PD participants will undergo a further biopsy. The investigators envisage enrolling a total of 25 participants and the investigators anticipate 30 months as a feasible time frame for accrual.

Being tested
Nivolumab
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • NivolumabDrug

    Also called Relatlimab

    Immunotherapy

Study groups in NCT03867799
Study groupRoleWhat they receive
Nivolumab and RelatlimabExperimentalNivolumab 480mg and Relatlimab 160mg will be administered intravenously every 4 weeks
Receives: Drug: Nivolumab

What is being measured

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

  1. Disease Control Rate (DCR)

    Measured: 6 months from treatment initiation

Secondary outcomes (6)

  1. NCI CTCAE version 5.0 toxicity

    Measured: within 30 days of the last dose of study treatment

  2. Disease Control Rate (DCR)

    Measured: 12 and 24 months

  3. Duration of disease control

    Measured: 6, 12 and 24 months

  4. Best Objective Response Rate

    Measured: 6, 12 and 24 months

  5. Progression Free Survival

    Measured: Time from registration to progression (radiological or clinical) or death at 6 months, 12 months and 24 months

  6. Overall survival

    Measured: time from registration to death from any cause at 6 months, 12 months and 24 months

Timeline

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

  1. First posted8 Mar 2019
  2. Study start27 Mar 2019
  3. Primary completion21 Oct 2022
  4. Study completionSep 2024 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03867799
Sponsor's protocol ID
CCR4938
Status last verified
Jun 2024
First submitted
30 Jan 2019
Last updated
14 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab in people with Metastatic Colorectal Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

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 13 inclusion and 36 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: status not confirmed, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

Disease Control Rate (DCR) (time frame: 6 months from treatment initiation). 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 NCT03867799.

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 14 Jun 2024.

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