Window-of-opportunity clinical trials platform for evaluation of novel treatment strategies in renal cell cancer.

Phase 1

• Conditions: Surgically resectable renal cell cancer (Stage M0/M1); MedDRA version: 21.0Level: PTClassification code 10038389Term: Renal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003056-21-GB
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-05
• Last Update Posted: 23 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
•Aged =18 years and over.
•Predicted life expectancy = 16 weeks.
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
••Have biopsy proven clear cell RCC.
••Allow access to archival FFPE tumour tissue from biopsy and nephrectomy.
••Have a surgically resectable tumour as determined by the treating Urologist
•T1b or above, any N status, M0, OR have any T or N status, M1 (but if M1, the participant must be deemed suitable for cytoreductive nephrectomy at time of enrolment).
•No prior exposure to PARP inhibitors, tyrosine kinase inhibitors, immunotherapy or immune checkpoint inhibitors, nor prior treatment with an mammalian target of rapamycin (mTOR) inhibitor. Prior cytokine therapy (eg, IL-2, IFN-a) or treatment with cytotoxics is allowed.
•At least 1 measurable lesion according to RECIST Version 1.1 at screening that can be accurately assessed at by MRI and is suitable for repeated assessment.
•Have adequate organ and marrow function
•Creatinine clearance =30mL/min (calculated by Cockcroft and Gault equation
•Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause (Protocol has further details of what this means- word count)
•For women of childbearing potential a negative serum pregnancy test must be performed within 28 days of study treatment and confirmed prior to treatment on day 1.
•Male patients must be willing to use a condom during treatment and for 3 months after the last dose of trial treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also be willing to use a highly effective form of contraception if they are of childbearing potential
•Patient is willing and able to comply with the protocol for the duration of the trial.
•Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
Some drug-specific Inclusion criteria apply, truncated due to word count

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38

Exclusion Criteria

•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 treatment.
•History of leptomeningeal carcinomatosis.
•Body weight =30kg
•Contraindication to cediranib, olaparib, durvalumab 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.
•History of hypersensitivity to active or inactive excipients of cediranib, olaparib or durvalumab.
•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- examples in Protocol- word count
•Major surgery within 4 weeks prior to first dose of trial drug (excluding placement of vascular access). If patientparticipants have undergone major surgery more than 4 weeks prior to the scheduled first dose of studytrial 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- see Protocol (word count)
•Any of the following within 12 months prior to trial entry:
omyocardial infarction,
ouncontrolled angina,
ocoronary/peripheral artery bypass graft,
osymptomatic congestive heart failure,
ocerebrovascular accident or transient ischemic attack,
operipheral arterial embolus.
•Current or prior use of immunosuppressive agents within 28 days prior to the of first day of trial drug, 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). See Protocol for exceptions (word count)
•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).
oParticipants 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 e

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified