CUP, Cancer of Unknown Primary
Conditions
Interventions
Trade Name: Keytruda
Product Name: Keytruda
Product Code: MK3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrol
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have measurable disease based on RECIST 1.1. 4. Be willing to provide consent for archival tumour (in the form of formalin fixed paraffin embedded (FFPE) block) or fresh tumour material (if judged technically feasible by radiologist is mandatory for diagnosis and biomarker analysis. 5. Have a performance status of 0 to 2 on the ECOG Performance Scale. 6. Cohort 1 - have had at least one prior line / regimen of chemotherapy appropriate for CUP, 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. Cohort 2 - be chemo-naïve for CUP (Previous chemotherapy for other cancers is allowed) 7. Adequate organ and bone marrow function - Absolute neutrophil count (ANC) = 1.5 x 109/L - Platelets = 100 x 109/L - Haemoglobin = 9 g/dL (=90 g/L) without transfusion or EPO dependency - Serum creatinine = 1.5 x Upper Limit of Normal (ULN) or Creatinine clearance = 60 mL/min for patients with creatinine levels > 1.5 x ULN - Serum total bilirubin = 1.5 x ULN or direct bilirubin = ULN for patients with total bilirubin levels >1.5 ULN - Aspartate aminotransferase [AST] = 2.5 x ULN (=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria will not be eligible for this study: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Hypersensitivity to pembrolizumab or any of its excipients. 5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. Has 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., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 10. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 11. Has an active infection requiring systemic therapy. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. Is pregnant or breastfeeding,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: What is the overall survival(OS) & Progression Free Survival (PFS) for the 1st cohort What is the overall response rates (OS) & Progression Free Survival (PFS)in a first-line setting for the 2nd cohort ; Secondary Objective: • Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in the second line setting • Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in Performance Status 2 (PS2) patients in any setting ; Primary end point(s): Primary Objectives and Hypothesis Objectives: In the context of the two sequential cohorts:- • Overall response rates by immune-related (irRECIST) and RECIST criteria in a second-line setting o Overall Survival (OS) & Progression Free Survival (PFS) • Overall response rates by immune-related (irRECIST) and RECIST criteria in a first-line setting o OS & PFS Hypothesis: Pembrolizumab has Efficacy in CUP • as a first-line treatment in terms of Response which translates into improved PFS and OS • as a second-line treatment in terms Response which translates into improved PFS and OS • and treatment leads to rapid improvement in quality of life (QOL) in high metastatic disease burden (in any line of therapy) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Objectives and Hypothesises Objective: • Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in the second line setting • Incidence of adverse events up to 8 weeks after the last dose of Pembrolizumab in Performance Status 2 (PS2) patients in any setting Hypothesis: • Pembrolizumab is much better tolerated than conventional chemotherapy in CUP patients and PS2 patients may also benefit. Exploratory Objective: • Identification of genomic biomarkers predictive of immune response to Pembrolizumab Hypotheses: • CUP patients have identifiable biomarkers predictive for Pembrolizumab efficacy • CUP patients have high mutational loads and this correlates with increased efficacy with Pembrolizumab | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Manager
Imperial College London
Outcome results
None listed