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Metastatic Renal Cell CarcinomaPhase 1/2CAPERNCT04262427

The CAPER Trial: A Phase Ib Clinical Trial of Cyclophosphamide And PEmbrolizumab in Metastatic Renal Cell Carcinoma

A Phase 1/2 study testing Cyclophosphamide 50mg and Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] in people with Metastatic Renal Cell Carcinoma, run by The Christie NHS Foundation Trust at 4 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 The sponsor has not verified this record for over two years, so it may be out of date.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

This is an open label investigator initiated Phase Ib study of combination pembrolizumab (Keytruda), 200mg IV 3 weekly (Q3W) with 50mg oral cyclophosphamide daily (OD) in metastatic renal cell carcinoma patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Cyclophosphamide 50mg and Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesUnited Kingdom
Study dates
28 Apr 2021to 28 Apr 2024
Phase
Phase 1/2
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

  • Participants are eligible to be included in the study only if all of the following criteria apply:
  • Histological confirmation of RCC of predominantly (>50%) clear cell type.
  • Presence of metastatic / locally advanced inoperable disease.
  • Current evidence of disease progression on immuno-oncology (IO) therapy as determined by CT / MRI imaging performed within 28 days prior to the first dose of study drug. Last dose of IO therapy must have been administered within 42 days prior to the first dose of study drug. IO therapy may consist of either:
  • First-line Ipilimumab / Nivolumab combination OR
  • Second / Third-line single agent Nivolumab OR
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  • Other PD-1 / PD-L1 / anti-CTLA-4 therapy within a clinical trial
  • Measurable disease according to RECIST version 1.1 criteria.
  • Site(s) of disease which are easily accessible and suitable for repeated biopsies (bone metastases are not suitable as a biopsy site).
  • Provision of archival tumour tissue sample (formalin-fixed paraffin embedded (FFPE) tissue blocks) and a newly obtained core or excisional biopsy of a tumour lesion not previously irradiated.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study drug.
  • Age > 18 years.
  • Have adequate organ function as defined below. Specimens must be collected within 14 days prior to the start of study treatment.
  • Absolute neutrophil count (ANC) ≥1.5 x109/L
  • Platelets ≥100 x109/L
  • Haemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
  • Creatinine ≤1.5 × Upper Limit of Normal (ULN) OR Measured or calculated creatinine clearance (CrCl) ≥30 mL/min for participant with creatinine levels OR (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl >1.5 × institutional ULN
  • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalised ratio (INR) OR prothrombin time (PT) / Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Able to take oral medications.
  • Life expectancy of > 6 months in the opinion of the investigator.
  • Male participants must agree to use a form of contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants are eligible to participate if they are not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
  • A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 180 days after the last dose of study treatment.
  • The participant provides written informed consent for the trial including consent to all samples.

Who cannot join

  • Participants are excluded from the study if any of the following criteria apply:
  • Treatment with more than one prior line of IO therapy (including previous standard of care and trial treatments).
  • High burden / symptomatic disease which in the opinion of the treating investigator requires Tyrosine Kinase Inhibitors (TKI) / alternative therapeutic approach.
  • Prior treatment with either pembrolizumab or cyclophosphamide.
  • Known severe hypersensitivity (≥Grade 3) to pembrolizumab, cyclophosphamide and/or any of their excipients.
  • Prior intolerance to IO therapy (any > Grade 2 toxicity which required permanent IO treatment discontinuation).
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  • Ongoing Adverse Events (AEs) due to previous therapies or surgery which have not resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisolone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the bladder / urothelial tract, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS (Central Nervous System) disease.
  • Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
  • Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • Known previous or current Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Note: no testing is required.
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Active infection requiring systemic therapy or has had requirement for antibiotics within 14 days prior to first dose of study treatment.
  • Known history of Human Immunodeficiency Virus (HIV). Note: no testing for HIV is required.
  • Known history of Hepatitis B (defined as Hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus (defined as HCV RNA positive) infection. Note: no testing for Hepatitis B and Hepatitis C is required.
  • Known history of active tuberculosis (Bacillus Tuberculosis, TB). Note: no testing for TB is required.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of trial treatment. Note: WOCBP must have a negative urine pregnancy test within 72 hours prior to trial entry (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

Trial locations and contacts

4 sites in 1 country.

CAPER Trial Coordinator contact

01517955289 ext. 01517955289

caper@liverpool.ac.uk

United Kingdom4 sites, 4 recruiting

  • Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust

    Cambridge

    Kate Fife

    Recruiting

  • Western General Hospital, NHS Lothian

    Edinburgh

    Stefan Symeonides

    Not yet recruiting

  • Royal Marsden Hospital NHS Foundation Trust

    London

    Andrew Furness

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester

    Tom Waddell

    Recruiting

Other trials in United Kingdom

About this study

Official title: The CAPER Study: A Phase Ib Clinical Trial of Cyclophosphamide And PEmbrolizumab in Metastatic Renal Cell Carcinoma (RCC) (CAPER Trial)

This is an open label investigator initiated Phase Ib study of combination pembrolizumab (Keytruda), 200mg IV 3 weekly (Q3W) with 50mg oral cyclophosphamide daily (OD) in metastatic renal cell carcinoma patients. 21 patients will be recruited within the United Kingdom (UK) will to examine the efficacy of the combination for up to 35 administrations (2 years). This study will be conducted in compliance with Good Clinical Practice (GCP) and all relevant regulations.

Read the detailed description

The CAPER Trial will be looking at patients with locally advanced (inoperable) or metastatic clear cell renal cell carcinoma who have had previous treatment with immunotherapy and have experienced disease progression. Immunotherapies aim to boost the body's natural defences to fight cancer, however the tumour micro-environment may significantly impact how effective this approach will be at reducing cancer growth and spread. The CAPER trial aims to evaluate whether oral metronomic cyclophosphamide (50mg once daily) can alter the tumour environment and ultimately lead to responses to pembrolizumab in patients who have failed prior immunotherapy.

Patients who join the study will initially take cyclophosphamide 50mg tablets once a day for 21 days during the 'run-in period'. Following this, they will continue with cyclophosphamide 50mg daily alongside intravenous pembrolizumab treatment administered once every 3 weeks. Patients will continue both treatments until the occurrence of either disease progression, unexpected toxicity, patient withdrawal, or completion of 24 months of treatment.

Patients will undergo CT scanning to evaluate response every 9 weeks during trial treatment.

Research biopsies will be taken at baseline (prior to treatment), after the 21 day run-in period on oral cyclophosphamide, and at the time of the first CT scan (week 9 on treatment). Patients will also have additional research blood samples collected at serial timepoints whilst on treatment. The biopsy and blood samples will allow evaluation of the changes induced by cyclophosphamide and pembrolizumab within the tumour microenvironment as well as changes in circulating factors such as cytokines.

Being tested
Cyclophosphamide 50mg, Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]
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.

  • Cyclophosphamide 50mgDrug

    Also called cyclophosphamide monohydrate

    cytotoxic chemotherapy

  • Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]Drug

    Also called Keytruda, MK-3475

    potent humanized immunoglobulin (Ig) G4 monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor

Study groups in NCT04262427
Study groupRoleWhat they receive
Single Group AssignmentExperimentalCyclophosphamide 50mg PO OD for 3 weeks as monotherapy followed by cyclophosphamide 50mg PO OD with pembrolizumab 200mg IV every 3 weeks
Receives: Drug: Cyclophosphamide 50mg; Drug: Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]

What is being measured

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

  1. Objective Response Rate (ORR)

    Occurrence of complete response or partial response as defined by RECIST v1.1 at any point in follow-up until end of study or death. Best Objective Response is the highest value achieved for each patient and will be used for the primary outcome analysis.

    Measured: From baseline up to 2 years, first documented progression or death

Secondary outcomes (3)

  1. Progression-Free Survival (PFS)

    To evaluate the median PFS in patients receiving cyclophosphamide and pembrolizumab in combination. PFS events are defined as either disease progression or death from any cause. The event date used for analysis will be the first occurrence of either disease progression or death and the analysis will use the following formula:

    Progression-free survival (months) = (exit date - date of first treatment)/30.4

    Measured: From the time of first treatment up to 2 years, the time of first documented progression, the censor date in months or death

  2. Overall Survival (OS)

    To evaluate the median OS in patients receiving cyclophosphamide and pembrolizumab in combination. OS events are defined as death from any cause. The event date used for analysis will be the confirmed date of death and the analysis will use the following formula:

    Overall Survival (months) = (Exit date - date of first treatment)/30.4

    Measured: From first treatment up to 2 years or death by any cause in months

  3. Incidence of treatment-emergent adverse events as assessed by occurrence of serious adverse events and adverse events of grade 3 severity and above

    To evaluate the safety profile of the combination of oral cyclophosphamide and pembrolizumab. The number of patients reporting Serious Adverse Events (SAEs) and Grade 3 or higher toxicity will be summarised overall and by preferred term (if severity is missing, the worst case will be assumed).

    Measured: From commencement of treatment to 30 days post cessation of treatment

Timeline

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

  1. First posted10 Feb 2020
  2. Study start28 Apr 2021
  3. Primary completion28 Oct 2023 (estimated)
  4. Study completion28 Apr 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04262427
Sponsor's protocol ID
CFTSp148
Other IDs
2018-004314-17, 2018
Acronym
CAPER
Status last verified
Aug 2022
First submitted
28 Jan 2020
Last updated
23 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide 50mg and Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] in people with Metastatic Renal Cell Carcinoma, run by The Christie NHS Foundation Trust at 4 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 27 inclusion and 22 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 23 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 CAPER Trial Coordinator (01517955289 ext. 01517955289, caper@liverpool.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From baseline up to 2 years, first documented progression or death). 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 NCT04262427.

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 23 Aug 2022.

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