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

NCT04262427 | Unknown Phase 1 DMC

• 2 other identifiers: CFTSp1482018-004314-17
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

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.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• 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

• Overall Survival (OS)

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

• 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

Study Arms (1)

Single Group Assignment

EXPERIMENTAL

Cyclophosphamide 50mg PO OD for 3 weeks as monotherapy followed by cyclophosphamide 50mg PO OD with pembrolizumab 200mg IV every 3 weeks

Drug: Cyclophosphamide 50mg; Drug: Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]

Interventions

Cyclophosphamide 50mg DRUG

cytotoxic chemotherapy

Also known as: cyclophosphamide monohydrate

Single Group Assignment

Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] DRUG

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

Also known as: Keytruda, MK-3475

Single Group Assignment

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator
• University of Liverpool: collaborator
• University of Manchester: collaborator

Study Sites (4)

Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

RECRUITING

Western General Hospital, NHS Lothian

Edinburgh, United Kingdom

NOT YET RECRUITING

Royal Marsden Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Cyclophosphamide; 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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Tom Waddell

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CAPER Trial Coordinator

CONTACT

01517955289; caper@liverpool.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: February 10, 2020
• Study Start: April 28, 2021
• Primary Completion: October 28, 2023
• Study Completion: April 28, 2024
• Last Updated: August 23, 2022

Record last verified: 2022-08

Locations

GB (4)