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Renal Cell CarcinomaPhase 2REFINENCT04913025

REduced Frequency ImmuNE Checkpoint Inhibition in Cancers

A Phase 2 study testing Nivolumab and Pembrolizumab in people with Renal Cell Carcinoma and Melanoma, run by University College, London at 3 sites 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 The sponsor has not verified this record for over two years, so it may be out of date.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

The REFINE trial aims to asses whether giving an immunotherapy drug less-often to patients with advanced cancer, results in fewer side effects whilst continuing to be an effective treatment. The question will be assessed in different tumour types by means of different cohorts within an overarching trial protocol. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma, Melanoma
What is being tested?
Nivolumab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
3 sitesUnited Kingdom
Study dates
26 May 2022to Apr 2025
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

None listed.

Who cannot join

  • Patients who have received ICI in a prior line of treatment.
  • Patients whose planned treatment is the combination of anti-PD-1 and tyrosine kinase inhibitor e.g. pembrolizumab+axitinib or the combination of traditional cytotoxic chemotherapy and anti-PD-1.
  • Patients with unresolved/untreated immune-related adverse events arising during the first 3 months treatment with standard of care ICI.
  • History of another previous malignancy, except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP.
  • Adequately treated non-melanoma skin cancer without evidence of disease.
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  • Adequately treated carcinoma in situ without evidence of disease.
  • Superficial bladder cancer.
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
  • Current or prior use of immunosuppressive medication within 14 days of starting trial treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.
  • Active infection including:
  • Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
  • Hepatitis B (known positive HBV surface antigen (HBsAg) result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
  • Hepatitis C. Note: Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Human immunodeficiency virus (positive HIV 1/2 antibodies).
  • Receipt of a live attenuated vaccine within 30 days prior to the start of treatment.
  • Note: Patients, if enrolled, should not receive a live vaccine while receiving immune checkpoint inhibitor and up to 30 days after the last dose of immune checkpoint inhibitor.
  • Known allergy or hypersensitivity to immune checkpoint inhibitor.
  • Pregnant or breastfeeding patients.
  • Uncontrolled adrenal insufficiency.
  • Any serious or uncontrolled medical or psychiatric disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, interfere with participation and/or compliance in the trial, or interfere with the interpretation of study results.
  • Participants who have undergone any prior systemic anti-cancer treatment (previous participation in adjuvant studies allowed, providing the patient was on the observation/ placebo arm - this may require un-blinding of the patient).
  • Untreated brain metastases or brain metastases treated only with whole brain radiotherapy. (Patients are eligible if previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT), or gamma knife with no subsequent evidence of progression and asymptomatic).

Trial locations and contacts

3 sites in 1 country.

Jonathan Badrock contact

02076704602

mrcctu.refine@ucl.ac.uk

United Kingdom3 sites, 3 recruiting

  • Addenbrooke's Hospital

    Cambridge, Cambridgeshire

    Amy Strong

    Brent O'Carriagan

    Recruiting

  • Castle Hill Hospital

    Hull, HU16 5JQ

    Paula O'Reilly

    Anthony Maraveyas

    Recruiting

  • The Christie

    Manchester

    Neha Sundar

    Tom Waddell

    Recruiting

Other trials in United Kingdom

About this study

Official title: REduced Frequency ImmuNE Checkpoint Inhibition in Cancers: A Multi Arm Phase II Basket Protocol Testing Reduced Intensity Immunotherapy Across Different Cancers

The REFINE trial aims to asses whether giving an immunotherapy drug less-often to patients with advanced cancer, results in fewer side effects whilst continuing to be an effective treatment. The question will be assessed in different tumour types by means of different cohorts within an overarching trial protocol.

Read the detailed description

In stage I eligible participants will be randomly assigned to either the standard interval (either 4 or 6 weeks) or the extended interval (either 8 or 12 weeks) following an initial 12 weeks of standard of care immunotherapy. Disease recurrence and survival will be assessed, along with quality of life and health economic outcomes. The trial includes a feasibility outcome by which recruitment feasibility will be assessed.

Immunotherapy drugs are a standard treatment option for advanced kidney cancer, melanoma, and some lung cancers. These drugs work by stimulating the body's own immune system to fight against cancer cells. Clinical trials have proven the effectiveness of immunotherapy drugs, such as ipilimumab, nivolumab or pembrolizumab, in the treatment of different cancers. However the best way to give these drugs is not known.

Medical subject headings
Carcinoma, Renal Cell, Melanoma

What participants receive

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

  • NivolumabDrug

    60-minute IV infusion, as a flat dose of 480mg

  • PembrolizumabDrug

    60-minute IV infusion, as a flat dose of 400mg

Study groups in NCT04913025
Study groupRoleWhat they receive
Standard intervalActive comparatorStandard of care regimen Nivolumab administered as an approximate 60-minute IV infusion, as a flat dose of 480mg once every 4 weeks OR Pembrolizumab administered as an approximate 60-minute IV infusion, as a flat dose of 400mg once every 6 weeks
Receives: Drug: Nivolumab; Drug: Pembrolizumab
Extended intervalExperimentalNivolumab administered as an approximate 60-minute IV infusion, as a flat dose of 480mg once every 8 weeks OR Pembrolizumab administered as an approximate 60-minute IV infusion, as a flat dose of 400mg once every 12 weeks
Receives: Drug: Nivolumab; Drug: Pembrolizumab

What is being measured

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

  1. Progression Free Survival

    Time to event

    Measured: 1 year 9 months follow-up

Secondary outcomes (8)

  1. Overall survival

    Measured from date of randomisation until date of death or last follow-up

    Measured: 1 year 9 months follow-up

  2. Quality of Life (QoL) - Generic

    EQ-5D-5L questionnaire to assess generic quality of life

    Measured: 1 year 9 months follow-up

  3. Treatment-related toxicity

    Measured using severity of all AEs and/or ARs (serious and non-serious) with the toxicity scales in NCI CTCAE v5.0 reviewed at the end of each stage and reported until trial closure

    Measured: 1 year 9 months follow-up

  4. Mean incremental cost per patient

    Measured using unit costs from NHS Reference Costs, Personal Social Services Research Unit (PSSRU) and British National Formulary (BNF) prices, and applying them to health and social care resource use collected via the Client Service Receipt Inventory (CSRI), intervention medication CRF, additional treatment logs, and concomitant medication CRF, every 12 weeks starting at baseline, calculating the cost and taking the difference between arms to calculate mean incremental cost per patient (bootstrapped regression, adjusting for baseline values, jointly with QALYs).

    Measured: 1 year 9 months follow-up

  5. Mean incremental quality-adjusted life-years (QALYs) per patient

    Measured using utility scores calculated from EQ-5D-5L questionnaire responses collected every 12 weeks starting at baseline, and applying them to the relevant period of follow-up to calculate quality-adjusted life-years (QALYs), and taking the difference between arms to calculate mean incremental QALYs per patient (bootstrapped regression, adjusting for baseline values, jointly with costs).

    Measured: 1 year 9 months follow-up

  6. Cost-utility analysis

    Assessing cost-effectiveness of reduced vs. standard frequency administration with summary result expressed as the incremental cost-effectiveness ratio (ICER), i.e. incremental cost per QALY gained, calculated by dividing incremental costs by incremental QALYs; with sensitivity analysis expressed via cost-effectiveness planes and cost-effectiveness acceptability curves to indicate probability that the intervention is cost-effective compared to the standard of care for a range of values of the cost-effectiveness threshold

    Measured: 1 year 9 months follow-up

  7. Feasibility of recruitment to each cohort

    Measured by sites completing screening logs to identify number of treatment cycles

    Measured: 1 year 9 months follow-up

  8. Quality of Life (QoL) - Cancer-specific

    EORTC QLQ-C30 questionnaire to assess cancer-specific quality of life

    Measured: 1 year 9 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 posted4 Jun 2021
  2. Study start26 May 2022
  3. Primary completionApr 2025 (estimated)
  4. Study completionApr 2025 (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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04913025
Sponsor's protocol ID
RF01
Other IDs
2021-002060-47
Acronym
REFINE
Status last verified
Sep 2022
First submitted
13 May 2021
Last updated
21 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Merrick S, Nankivell M, Quartagno M, Clarke CS, Joharatnam-Hogan N, Waddell T, O'Carrigan B, Seckl M, Ghorani E, Banks E, Edmonds K, Bray G, Woodward R, Bennett R, Badrock J, Hudson W, Langley RE, Vasudev N, Pickering L, Gilbert DC. REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers. Contemp Clin Trials. 2023 Jan;124:107030. doi: 10.1016/j.cct.2022.107030. Epub 2022 Nov 26.

    PubMed 36519749

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Pembrolizumab in people with Renal Cell Carcinoma and Melanoma, run by University College, London at 3 sites 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 0 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: status not confirmed, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Contact Jonathan Badrock (02076704602, mrcctu.refine@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 1 year 9 months follow-up). 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 NCT04913025, which also lists 1 linked publication.

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 21 Sep 2022.

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