REduced Frequency ImmuNE Checkpoint Inhibition in Cancers

NCT04913025 | Unknown Phase 2 DMC

• 2 other identifiers: RF012021-002060-47
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Renal Cell Carcinoma; Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time to event

  1 year 9 months follow-up

Secondary Outcomes (8)

• Overall survival

  1 year 9 months follow-up

• Quality of Life (QoL) - Generic

  1 year 9 months follow-up

• Treatment-related toxicity

  1 year 9 months follow-up

• Mean incremental cost per patient

  1 year 9 months follow-up

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

  1 year 9 months follow-up

Study Arms (2)

Standard interval

ACTIVE COMPARATOR

Standard 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

Drug: Nivolumab; Drug: Pembrolizumab

Extended interval

EXPERIMENTAL

Nivolumab 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

Drug: Nivolumab; Drug: Pembrolizumab

Interventions

Nivolumab DRUG

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

Extended interval; Standard interval

Pembrolizumab DRUG

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

Extended interval; Standard interval

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• WHO Performance Status 0 or 1.
• Patients with locally advanced or metastatic cancer whose clinician has determined they are candidates for treatment with standard of care immune checkpoint inhibitor.- Patients aged ≥18years.
• Adequate normal organ and marrow function:
• Haemoglobin ≥9.0g/dL (transfusions will be allowed within 2 weeks prior to randomisation in order to achieve the entry criteria).
• Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).
• Platelet count ≥100 x 109/L (≥100,000 per mm3).
• Bilirubin ≤1.5 x ULN (This will not apply to subjects with confirmed Gilbert's syndrome (i.e., persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be considered eligible only in consultation with their physician).
• AST/ALT ≤3 x ULN.
• eGFR \>40mL/min by CKD-EPI formula .
• Both men and women enrolled in this trial must be in agreement with trial policy on contraception during the treatment phase of the study. Egg donation, sperm donation and breastfeeding must be avoided.
• Evidence of post-menopausal status or negative serum HCG pregnancy test for female pre/peri-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormone treatments and if they have luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilisation (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Patients with unresectable locally-advanced or metastatic renal cell carcinoma (including clear cell and papillary histologies).
• Intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University College, London: lead
• JP Moulton Charitable Foundation: collaborator

Study Sites (3)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

RECRUITING

Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

RECRUITING

The Christie

Manchester, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 36519749 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma

Interventions

Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Duncan Gilbert

  MRC CTU at UCL

  STUDY DIRECTOR

Central Study Contacts

Jonathan Badrock

CONTACT

02076704602; mrcctu.refine@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: June 4, 2021
• Study Start: May 26, 2022
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)