Trial of Pembrolizumab in Cancer of Unknown Primary (CUPem)
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|ClinicalTrials.gov Identifier: NCT03752333|
Recruitment Status : Recruiting
First Posted : November 26, 2018
Last Update Posted : March 1, 2019
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
|Condition or disease||Intervention/treatment||Phase|
|Cancer of Unknown Primary Site||Drug: Pembrolizumab||Phase 2|
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 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 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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||77 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Two-Stage, Trial of Pembrolizumab in Cancer of Unknown Primary|
|Actual Study Start Date :||February 22, 2019|
|Estimated Primary Completion Date :||May 30, 2022|
|Estimated Study Completion Date :||November 30, 2022|
All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).
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.
Other Name: Keytruda
- Overall response rates by immune-related (irRECIST) and RECIST criteria in a second-line & first-line setting [ Time Frame: 6 months (based on average length of treatment per patient) ]
Pembrolizumab has Efficacy in CUP
- as a first-line treatment in terms of Response which translates into improved progression-free survival (PFS) and overall survival (OS)
- as a second-line treatment in terms Response which translates into improved PFS and OS
- and treatment leads to rapid improvement in QOL in high metastatic disease burden (in any line of therapy)
- Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in the second line setting [ Time Frame: 6-8 months (based on average length of treatment per patient ]Pembrolizumab is much better tolerated than conventional chemotherapy in CUP patients and PS2 patients may also benefit.
- Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in Performance Status 2 (PS2) patients in any setting [ Time Frame: 6-8 months (based on average length of treatment per patient) ]• Pembrolizumab is much better tolerated than conventional chemotherapy in CUP patients and PS2 patients may also benefit.
- Identification of potential genomic biomarkers predictive of immune response to Pembrolizumab [ Time Frame: 12 months (post study completion) ]This would be a retrospective analysis of blood samples collected for future research purposes only. Research bloods will be used to examine DNA and measure various blood biomarkers. These biomarkers may predict possible response to study treatment. As these samples are being taken before, during and after treatment, they will help us understand how the study treatments work. This will also enable us to learn whether or not the treatments have the desired effect, and to understand if these effects may be beneficial for the treatment of cancer of unknown primary (CUP). This information may also be used to develop and test other new treatments in the future. The panel of potential biomarkers against which the blood plasma will be tested has not been established yet. Information gained from this research component is not directly beneficial to patients taking part in this clinical trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03752333
|Contact: Mohana Suppiah, BSc, MScfirstname.lastname@example.org|
|Study Chair:||Harpreet Wasan, MBBS, FRCP||Imperial College London|