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Renal Cell CancerPhase 2WIRENCT03741426

WIRE - Novel Treatments in Renal Cell Cancer

A Phase 2 study testing Olaparib, Cediranib and Volrustomig in people with Renal Cell Cancer, run by CCTU- Cancer Theme at 7 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Evaluation of proof of mechanism with relation to ktrans and/or CD8 count when different IMPs are given as monotherapy or as combination therapy. These would be administered in the "window of opportunity", prior to nephrectomy in surgically resectable renal cell cancer Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Cancer
What is being tested?
Olaparib, Cediranib and Volrustomig
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
7 sitesUnited Kingdom
Study dates
27 Jul 2020to 30 Dec 2027
Phase
Phase 2
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

None listed.

Who cannot join

  • cT1a N0 M0-staged Renal Cell Cancer
  • Participants with brain metastases. A scan to confirm the absence of brain metastases is not required.
  • Participants with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days prior to start of first dose of treatment.
  • History of leptomeningeal carcinomatosis.
  • Body weight ≤30kg
  • Contraindication to cediranib, olaparib, volrustomig and rilvegostomig or chimeric or humanized antibodies or fusion proteins (specifically participants with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not enter the trial).
Show all 73Show fewer
  • History of hypersensitivity to active or inactive excipients of cediranib, olaparib or volrustomig and rilvegostomig.
  • Other invasive malignancy within the last 2 years. Participants with previous history of malignancies with a negligible risk of metastasis or death and treated with expected curative intent are eligible at discretion of clinical team, for example:
  • Carcinoma in situ of the cervix.
  • Basal or squamous cell skin cancer.
  • Localized low to intermediate risk prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse; or prostate cancer (Stage T1/T2a, Gleason ≤ 6 and PSA < 10 ng/mL) undergoing active surveillance and treatment naïve.
  • Major surgery within 4 weeks prior to first dose of trial drug (excluding placement of vascular access). If participants have undergone major surgery more than 4 weeks prior to the scheduled first dose of trial drug, they must have fully recovered from the procedure.
  • Minor surgery (not including the diagnostic biopsy) within 2 weeks prior to first dose of trial treatment
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Concurrent enrolment in another clinical trial unless it is an observational (non-interventional NOT involving CTIMPs) or translational clinical trial, or during the follow-up period of an interventional clinical trial.
  • Receipt of the last dose of anticancer therapy or radiotherapy, chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolisation, monoclonal antibodies) ≤28 days prior to the first dose of trial drug.
  • Gastrointestinal abnormalities including:
  • o refractory nausea and vomiting,
  • inability to take oral medication;
  • requirement for intravenous alimentation;
  • prior surgical procedures affecting absorption including total gastric resection;
  • treatment for active peptic ulcer disease in the past 6 months prior to the first dose of trial treatment;
  • active gastrointestinal bleeding, unrelated to cancer, as evidenced by haematemesis, haematochezia or melaena in the past 120 days prior to the first dose of trial treatment without evidence of resolution documented by endoscopy or colonoscopy;
  • malabsorption syndromes.
  • Any of the following within 12 months prior to trial consent:
  • o myocardial infarction,
  • o clinically significant arrhythmia,
  • uncontrolled angina,
  • coronary/peripheral artery bypass graft,
  • symptomatic congestive heart failure,
  • cerebrovascular accident or transient ischemic attack,
  • peripheral arterial embolus.
  • Current or prior use of immunosuppressive agents within 28 days prior to the first dose of trial treatment, including anti-TNF and anti-IL17 agents, with the exceptions of intranasal or inhaled corticosteroids, or systemic corticosteroids at physiological doses which are not to exceed 10mg/day prednisolone (or an equivalent corticosteroid). The following exceptions are allowed:
  • o Intranasal, inhaled, topical or local steroid injections (e.g. intra articular injection).
  • Systemic corticosteroids at physiological doses not to exceed 10mg/day prednisolone (or equivalent).
  • Steroids for premedication of hypersensitivity reactions (e.g. as CT scan premedication).
  • Immunocompromised participants (e.g., participants who are known to be serologically positive for human immunodeficiency virus (HIV) or have a history of active primary immunodeficiency).
  • Active infection including tuberculosis (clinical history, physical examination and radiographic findings, and Tuberculosis (TB) testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV1/2 antibodies).
  • o Participants with a past or resolved HBV infection (defined as: presence of hepatitis B core antibody -anti-HBc- and absence of hepatitis B surface antigen -HbsAg-) are eligible.
  • As judged by the Investigator, any participant considered a high medical risk, for example due to a serious uncontrolled medical or psychiatric disorder, non-malignant systemic disease or on-going or active infection.
  • Persistent toxicities (≥Common Terminology Criteria for Adverse Event (CTCAE V5.0) grade 2) caused by previous cancer therapy, excluding alopecia and vitiligo.
  • o Participants with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Chief Investigator.
  • Participants with contraindication to MRI including; contraindicated metallic implants, contraindicated coronary stents and pacemakers. Inability to lie flat or still in an MRI scanner for whatever reason (e.g., claustrophobia).
  • Judgement by the Investigator that the participant should not participate in the trial.
  • Involvement in the planning and/or conduct of the trial.
  • SPECIFIC EXCLUSION CRITERIA FOR CEDIRANIB AND/OR OLAPARIB CONTAINING ARMS:
  • Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors, or inducers or substrates for CYP1A2 (see Section 10.7 Concomitant therapy and Appendices 4 and 5 for full details).
  • Concomitant medications known to prolong the QT interval (see Appendices 4\& 5) or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age), history of Torsades de pointes.
  • Resting ECG indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator (e.g., unstable ischaemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500ms, electrolyte disturbances, resting QTc of ≥470ms (Fridericia; as per local reading), etc.) on two or more time points within a 24-hour period or family history of long QT syndrome.
  • Requirement of anticoagulant therapy with oral vitamin K antagonists. o Therapeutic use of low molecular weight heparin is allowed.
  • Poorly controlled hypertension (persistently elevated > 150/100mmHg (or > 140/90 FOR OLAPARIB PLUS CEDIRANIB ARM ONLY), either systolic or diastolic or both, despite anti-hypertensive medication)
  • Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
  • History of intra-abdominal abscess within 3 months prior to starting the first dose of trial treatment
  • History of GI perforation. Participants with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting the first dose of trial treatment, and participant is deemed to be at low risk of recurrent fistula.
  • SPECIFIC EXCLUSION CRITERIA FOR CEDIRANIB MONOTHERAPY OR CEDIRANIB- CONTAINING ARMS ONLY:
  • Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per institutional guidelines, or <55%, if threshold for normal not otherwise specified by institutional guidelines, for participants with the below risk factors (an Echocardiogram should be performed at baseline and if clinically indicated):
  • o Prior treatment with anthracyclines
  • Prior treatment with trastuzumab
  • Prior central thoracic RT, including exposure of heart to therapeutic doses of ionising RTM
  • Prior history of other significant impaired cardiac function
  • SPECIFIC EXCLUSION CRITERIA FOR VOLRUSTOMIG AND RILVEGOSTOMIG ARMS ONLY:
  • Participant with irreversible toxicity not reasonably expected to be exacerbated by treatment with volrustomig and rilvegostomig may be included only after consultation with the Trial Oncologist.
  • History of organ transplant that requires use of immunosuppressive medications or any medical condition in which immunosuppressive agents were administered, including but not limited to: systemic corticosteroids, methotrexate, azathioprine.
  • Receipt of live, attenuated vaccine within the last 30 days. Note: enrolled participants should not receive live, attenuated vaccine while receiving volrustomig or rilvegostomig nor within 30 days of last dose of volrustomig or rilvegostomig.
  • Active or prior documented autoimmune or inflammatory disorders (except vitiligo), for example:
  • Intestinal: Inflammatory Bowel Disease (Colitis (including ulcerative colitis), Crohn's Disease), Diverticulitis, Coeliac Disease (except participants with coeliac disease controlled by diet alone),
  • Vascular: any type of vasculitic disorder, e.g. Wegener syndrome, granulomatosis with polyangiitis.
  • Endocrine: any endocrine alteration related to an autoimmune process e.g. Hashimoto syndrome, Grave's disease. NOTE: participants with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement treatment may be included.
  • Respiratory: Active Pneumonitis (of any origin: inflammatory or infectious), Sarcoidosis syndrome.
  • Dermatological: Psoriasis, Lupus/SLE (unless the skin condition has never required systemic therapy).
  • Other: Rheumatoid Arthritis, Hypophysitis, Uveitis.
  • Participants with autoimmune conditions without active disease in the past 5 years may be included but only after discussion with the Trial Oncologist.
  • Participants with persistent toxicities (≥Common Terminology Criteria for Adverse Event (CTCAE v 5.0) grade 2) caused by previous cancer therapy, excluding alopecia and vitiligo, which are not reasonably expected to be exacerbated by treatment with volrustomig and rilvegostomig may be included only after consultation with the Chief Investigator.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

CCTU Cancer Theme contact

01223 256364 ext. 256364

cuh.ccturegulatory@nhs.net

Sulekha Said contact

01223 256364 ext. 256364

cuh.wire@nhs.net

7 sites in 1 country

United Kingdom7 sites, 7 recruiting

  • Addenbrooke's Hospital

    Cambridge, England, CB2 2QQ

    Recruiting

  • Western General Hospital, Edinburgh, EH4 2XU

    Edinburgh

    Alex Laird

    Recruiting

  • Royal Devon University Healthcare NHSFT, Exeter, EX2 5DW

    Exeter

    Sarah Welsh

    Recruiting

  • Beatson Institute for Cancer Research

    Glasgow

    Ailsa Griffin, Ailsa.Griffen@glasgow.ac.uk

    Balaji Venugopal

    Recruiting

  • Imperial College Healthcare NHS Trust

    London

    Naveed Sarwar

    Recruiting

  • Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE

    Oxford

    Mark Sullivan

    Recruiting

  • Weston Park Hospital

    Sheffield

    Janet Brown

    Not yet recruiting

Other trials in United Kingdom

About this study

Official title: WIndow of Opportunity Clinical Trials Platform for Evaluation of Novel Treatments Strategies in REnal Cell Cancer

Evaluation of proof of mechanism with relation to ktrans and/or CD8 count when different IMPs are given as monotherapy or as combination therapy. These would be administered in the "window of opportunity", prior to nephrectomy in surgically resectable renal cell cancer

Read the detailed description

A Phase 2, multi-arm, multicentre, non-randomised, proof-of-mechanism (single and combination IMPs) trial using a Bayesian adaptive design.

A multi-centre trial. 2 centres initially planned - this may be reduced or increased in order to recruit the required number of participants.

Up to sixty (60) patients with surgically resectable renal cell cancer (Stage M0/M1). Up to twelve (12) participants will be registered for each of the single oral IMP arms, up to twenty (20) participants for the combination treatment arm(s) and for the single IV infusion IMP arms as per the Bayesian adaptive design.

The trial duration consists of a 28 day screening period, a minimum of 2 weeks oral IMP (Olaparib and/or Cediranib) treatment or a single dose of durvalumab alone or in combination in the window-of-opportunity period prior to surgery (nephrectomy or partial nephrectomy) performed as standard of care.

Participants will continue oral IMP treatment up until surgery (stopping when indicated for surgical safety reasons). As such treatment duration will be variable and an optional 21 day telephone assessment will take place for patients who remain on IMP. Patients will then be reviewed in the surgical follow-up clinic at 6 weeks and 3 months post-surgery as standard of care.

For patients on monotherapy or combination Olaparib and Cediranib IMP, response will be measured using DCE-MRI (Ktrans), defining reduced tumour capillary permeability.

For patients on monotherapy Volrustomig and Rilvegostomig, response will be measured using CD8 positive T cells.

Additional safety outcomes will be assessed, along with the tumour response and various biological measures that would indicate drug mechanistic response.

Being tested
Olaparib, Cediranib, Volrustomig, Rilvegostomig
Keywords
Olaparib, Cediranib, Volrustomig, Rilvegostomig
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • OlaparibDrug

    Also called AZD2281, KU-0059436, LYNPARZA

    Olaparib 300mg twice daily, oral medication administered for at least 2 weeks and up until the morning of nephrectomy. Arms 2, 3 and 5

  • CediranibDrug

    Also called AZD2171

    Cediranib 20mg once daily, oral medication administered for at least 2 weeks until 36 hours prior to nephrectomy. Arms 1 and 3

  • VolrustomigDrug

    Also called MEDI5752

    Volrustomig- 750mg intravenous infusion once, a maximum of 5 weeks prior to nephrectomy.

  • RilvegostomigDrug

    Also called AZD2936

    Rilvegostomig- 750mg intravenous infusion once, a maximum of 5 weeks prior to nephrectomy.

Study groups in NCT03741426
Study groupRoleWhat they receive
Arm 1- CediranibExperimentalCediranib tablet oral 20mg once daily for a minimum of 2 weeks up until 36 hours before nephrectomy.
Receives: Drug: Cediranib
Arm 2- OlaparibExperimentalOlaparib tablet oral 300mg twice daily for a minimum of 2 weeks up until the morning of nephrectomy.
Receives: Drug: Olaparib
Arm 3- Olaparib and CediranibActive comparatorOlaparib tablet oral 300mg twice daily for a minimum of 2 weeks up until the morning of nephrectomy AND Cediranib tablet oral 20mg once daily for a minimum of 2 weeks up until 36 hours before nephrectomy.
Receives: Drug: Olaparib; Drug: Cediranib
Arm 4- VolrustomigExperimentalVolrustomig- 750mg intravenous infusion once, a maximum of 5 weeks prior to nephrectomy.
Receives: Drug: Volrustomig
Arm 5- RilvegostomigExperimentalRilvegostomig- 750mg intravenous infusion once, a maximum of 5 weeks prior to nephrectomy.
Receives: Drug: Rilvegostomig

What is being measured

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

  1. Proof-of-Mechanism (ktrans): to assess for 30% ktrans change between pre-IMP treatment and IMP End of Treatment DCE-MRI

    Cediranib and Olaparib single IMP, Cediranib and Olaparib in combination IMP arms, having received at least 14 days' worth of IMP

    Measured: Change between Screening and 72 hours before surgery

  2. Proof-of-Mechanism (CD8): to assess for 30% change between pre-IMP treatment and IMP End of Treatment in CD8 positive T-cells. This will be based on IHC assessment via histoscore

    Volrustomig and Rilvegostomig, single dose of IMP

    Measured: Change between Screening and 72 hours before surgery

Secondary outcomes (3)

  1. Number of participants with, and severity of, Adverse Events

    AEs are graded for severity according to the CTCAE toxicity criteria (Version 5.0)

    Measured: From consent to 3 months post-surgery

  2. Change in primary tumour size assessed by DCE-MRI

    Change in primary tumour size assessed by DCE-MRI

    Measured: Between days -28 to 0 and 72 hrs before surgery, having received at least 2 weeks' worth of IMP

  3. Tumour Response

    Assessment of tumour response according to RECIST 1.1

    Measured: Between days -28 to 0 for all patients.At 72 hrs before surgery if metastases are present,having received at least 2 wks' worth of IMP).Then every 8 wks until end of study (study ends=3 mths post surgery) or until progression

Timeline

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

  1. First posted14 Nov 2018
  2. Study start27 Jul 2020
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion30 Dec 2027 (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
Basic science
Allocation
Non-randomised
Intervention model
Sequential
Model description
Bayesian Adaptive
Masking
None (open label)
Enrolment
134 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03741426
Sponsor's protocol ID
WIRE
Acronym
WIRE
Status last verified
Sep 2026
First submitted
31 Oct 2018
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Horvat-Menih I, McLean MA, Birchall J, Zamora Morales MJ, Wylot M, Ursprung S, Woitek R, Serrao E, Grimmer A, Latimer E, Khan AS, Priest AN, Gill AB, Kaggie JD, Graves MJ, Barrett T, Wason JM, Mossop H, Thomas M, Said S, Warren AY, Fife K, Eisen T, Matakidou A, Ince W, O'Carrigan B, Jones JO, Welsh SJ, Mitchell TJ, Armitage JN, Riddick AC, Stewart GD, Gallagher FA. Evaluating the metabolic effects of neoadjuvant treatment in clear cell renal cell carcinoma using hyperpolarized [1-13 C]pyruvate MRI. Abdom Radiol (NY). 2026 Jul;51(7):3557-3562. doi: 10.1007/s00261-025-05313-z. Epub 2025 Dec 10.

    PubMed 41369900

  • Horvat-Menih I, Li H, Priest AN, Li S, Gill AB, Mendichovszky IA, Francis ST, Warren AY, O'Carrigan B, Welsh SJ, Jones JO, Riddick ACP, Armitage JN, Mitchell TJ, Stewart GD, Gallagher FA. High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades. Eur Radiol Exp. 2024 Jul 10;8(1):76. doi: 10.1186/s41747-024-00476-8.

    PubMed 38981998

  • Ursprung S, Mossop H, Gallagher FA, Sala E, Skells R, Sipple JAN, Mitchell TJ, Chhabra A, Fife K, Matakidou A, Young G, Walker A, Thomas MG, Ortuzar MC, Sullivan M, Protheroe A, Oades G, Venugopal B, Warren AY, Stone J, Eisen T, Wason J, Welsh SJ, Stewart GD. The WIRE study a phase II, multi-arm, multi-centre, non-randomised window-of-opportunity clinical trial platform using a Bayesian adaptive design for proof-of-mechanism of novel treatment strategies in operable renal cell cancer - a study protocol. BMC Cancer. 2021 Nov 18;21(1):1238. doi: 10.1186/s12885-021-08965-4.

    PubMed 34794412

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib, Cediranib and Volrustomig in people with Renal Cell Cancer, run by CCTU- Cancer Theme at 7 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 73 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: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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?

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?

Contact CCTU Cancer Theme (01223 256364 ext. 256364, cuh.ccturegulatory@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proof-of-Mechanism (ktrans): to assess for 30% ktrans change between pre-IMP treatment and IMP End of Treatment DCE-MRI (time frame: Change between Screening and 72 hours before surgery). The study lists 2 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 NCT03741426, which also lists 3 linked publications.

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 25 Sep 2026.

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