Trial of Pembrolizumab in Cancer of Unknown Primary — CUPem  

Cancer of Unknown Primary Site Clinical Trial

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

Status Active, not recruiting

Clinical Trial 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

Clinical Trial 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). ;

Related Conditions & MeSH terms

• Cancer of Unknown Primary Site
• Neoplasms, Unknown Primary

• NCT number: NCT03752333
• Study type: Interventional
• Source: Imperial College London
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 22, 2019
• Completion date: September 30, 2024