A Phase II, Two-Stage, Trial of Pembrolizumab in Cancer of unknown primary

Phase 1

• Conditions: CUP, Cancer of Unknown Primary; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001327-39-GB
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-19
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 77

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 (< 5 x ULN if liver metastases are present)
- Alanine aminotransferase [ALT]) = 2.5 x ULN (< 5 x ULN if liver metastases are present)
- Albumin = 2.5g/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN
- Activated Partial Thromboplastin Time (APTT) =1.5 X ULN (unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

8.Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
9.Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 6.9.2 – Contraception, for the course of the study through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
10.Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.9.2 - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 37

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,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified