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

Phase 1

• Conditions: Metastatic Renal Cell Carcinoma
• Interventions: Drug: Cyclophosphamide 50mg; Drug: Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]

• Registration Number: NCT04262427
• Lead Sponsor: The Christie NHS Foundation Trust

Brief 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. 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.

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.

Study Timeline

• Study First Submitted: 2020-01-28
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-10
• Study Start: 2021-04-28
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-22
• Last Update Posted: 2022-08-23
• Primary Completion: 2023-10-28
• Study Completion: 2024-04-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Group Assignment	Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]	Cyclophosphamide 50mg PO OD for 3 weeks as monotherapy followed by cyclophosphamide 50mg PO OD with pembrolizumab 200mg IV every 3 weeks
Single Group Assignment	Cyclophosphamide 50mg	Cyclophosphamide 50mg PO OD for 3 weeks as monotherapy followed by cyclophosphamide 50mg PO OD with pembrolizumab 200mg IV every 3 weeks

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	From baseline up to 2 years, first documented progression or death	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From first treatment up to 2 years or death by any cause in months	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
Incidence of treatment-emergent adverse events as assessed by occurrence of serious adverse events and adverse events of grade 3 severity and above	From commencement of treatment to 30 days post cessation of treatment	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).
Progression-Free Survival (PFS)	From the time of first treatment up to 2 years, the time of first documented progression, the censor date in months or death	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

Trial Locations

Locations (4)

Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom

Western General Hospital, NHS Lothian; 🇬🇧 Edinburgh, United Kingdom

Royal Marsden Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom