NCT03752333

Trial of Pembrolizumab in Cancer of Unknown Primary

A Phase II, Two-Stage, Trial of Pembrolizumab in Cancer of Unknown Primary

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (actual)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Abbreviated Title : CUPem Clinical Indication : A Phase II, Two-Stage, Trial of Pembrolizumab in Cancer of unknown primary Trial Type : Single Arm, non-randomised; Two-stage; Hypothesis generating Type of control : None Route of administration : IV Trial Blinding : N/A Treatment Groups :Two cohorts: (i) First Cohort: One or more lines of prior therapy (ii) Second Cohort: First Line untreated CUP patients Number of trial subjects : i) First Cohort: 20 ii) Second Cohort: 57 Eligibility Criteria : The Eligibility Criteria are the same as used in the A trial of chemotherapy for cancer of unknown primary (CUP-ONE) trial in the United Kingdom (UK), please see below. * Histologically confirmation of a diagnosis of CUP, with imaging and all diagnostic investigations confirmed as CUP within a CUP Multidisciplinary Team (MDT). * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Patients must have disease that is not amenable to potentially curative options such as resection or radical radiotherapy * If patient's disease presentation precludes tumour biopsy (inaccessible or biopsy thought not to be in the patient's best interest), the patient is not study eligible. Estimated recruitment period : 2 years Estimated duration of trial : 3.9 years including set up, recruitment, follow up and close down. Duration of Participation : Cohort 1 = 6-8 months; Cohort 2 = 8-18 months Estimated average length of treatment per patient =6 months

Detailed description

An open label, non-randomised, single arm, sequential phase (two sequential cohorts) study, evaluating the preliminary efficacy of Pembrolizumab in Cancer of unknown Primary (CUP). Cohort 1: Cohort 1 will enrol a maximum of 20 patients, who have had at least one prior line / regimen of chemotherapy (at least 2 cycles) appropriate for CUP and who have not had a RECIST response to first-line chemotherapy, or are progressing after an initial response, or are treatment intolerant to first-line chemotherapy, due to unacceptable toxicity. As soon as there has been one documented response in cohort 1, the study then proceeds to enrol cohort 2 in parallel. Cohort 2 will not be initiated, if have been no cohort 1 (0/20) patients who have benefitted and 20 cohort 1 patients have completed at least 12 weeks of therapy. Benefit for this study is defined as either a RECIST or irRECIST response; stable disease for a minimum of 12 weeks. This allows a go / no-go decision to proceed/ not proceed to enrolling cohort 2 by the trial management group Cohort 2: Cohort 2 will enrol a maximum of 57 patients who are chemo-naïve (first-line setting) for CUP\*, with a PS 0-2. Benefit for this study is defined as either a RECIST or irRECIST response or stable disease at 12 weeks. \*Previous chemotherapy for other cancers is allowed For both cohorts, patients will undergo screening procedures during a standard 28-days time window from initiation of the study, under standard Good Clinical Practice (GCP) and informed consent. Restaging will be performed by computerized tomography using ir-RECIST criteria at 3 months from initiation of systemic treatment and on an 8 weekly basis thereafter until radiological proven disease progression or intolerance or patient choice. The EORTC Quality of Life Questionnaire (QLQ-C30) questionnaire (to assess the quality of life) will be done at baseline after 3 months and then at discontinuation of study treatment. Correlative translational study samples (blood) and tissue (used for histological confirmation and to document Programmed Death-Ligand 1 (PD-L1) expression) will be collected at baseline, and blood and serum samples monthly (after an informed optional consent and banked for retrospective immune-modulating and other biomarkers for future research and analysis).

Conditions

• Cancer of Unknown Primary Site

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.

Timeline

• Start date: 2019-02-22
• Primary completion: 2025-03-31
• Completion: 2025-03-31
• First posted: 2018-11-26
• Last updated: 2026-01-22

Locations

3 sites across 1 country: United Kingdom