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Carcinoma of Unknown PrimaryPhase 2CUPNCT03391973

Pembrolizumab in Patients With Poor-Prognosis Carcinoma of Unknown Primary Site (CUP)

A Phase 2 study testing Pembrolizumab Injection in people with Carcinoma of Unknown Primary, run by AHS Cancer Control Alberta at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Abbreviated Title: Pembrolizumab in Patients with Poor-Prognosis Carcinoma of Unknown Primary Site (CUP) Trial Phase: 2 Clinical Indication: Treatment naïve patients with poor prognosis carcinoma of unknown primary site Trial Type: Single arm phase 2 Type of control: Not applicable Route of administration: Intravenous… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Carcinoma of Unknown Primary
What is being tested?
Pembrolizumab Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesCanada
Study dates
24 Aug 2018to 12 Feb 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Have histologically (or cytologically) documented, metastatic carcinoma with no primary site identified. The following tests are required to exclude a primary site of disease: complete history and physical examination, blood chemistry (including serum tumor marker for prostate-specific antigen (PSA) in men, alpha-fetoprotein (AFP), β-human chorionic gonadotropin (β-hCG)) and mammography in women, urinalysis, thoracic and abdominopelvic computed tomography scans, bone scan, and symptom or sign-oriented imaging or endoscopic studies).
  • Have adenocarcinoma, a poorly differentiated carcinoma, or any squamous cell carcinomas.
  • Be willing and able to provide written informed consent for this trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have documented measurable disease based on RECIST 1.1. via Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI).
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 calendar days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived Formalin-Fixed, Paraffin-Embedded (FFPE) Block(s).
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  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Must have a documented negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication if female and of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
  • Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity from the time they sign the informed consent form prior to start of therapy through 120 calendar days after the last dose of study medication. Subjects of childbearing potential are defined as those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects must agree to use 2 adequate methods of contraception from the time they sign the informed consent form prior to start of therapy through 120 calendar days after the last dose of study therapy. Examples include: condoms, spermicidal jelly, and abstinence.
  • Demonstrate adequate organ function as defined in Table 1 below. All screening labs must be performed within 7 calendar days of treatment initiation.

Who cannot join

  • CUP suspected to be lymphomas (e.g. staining for leukocyte common antigen), malignant melanoma (e.g. staining for both S100 and HMB45), extragonadal germ cell neoplasms (e.g. staining for both AFP and β-hCG), sarcomas (e.g. staining for cytokeratins and vimentin), neuroendocrine tumors (e.g. staining for chromogranin and synaptophysin), and prostatic adenocarcinomas in men (e.g. staining for PSA).
  • Patient subgroups that are suitable for well-defined treatments: (e.g. women with adenocarcinoma involving axillary lymph nodes as the only site of disease, women with papillary serous carcinoma of the peritoneum, patients with squamous cell carcinoma that involved either cervical or inguinal lymph nodes only, patients with poorly differentiated carcinomas that suggested germinal tumors and with elevated levels of β-hCG and/or AFP, and patients with carcinoma that involved a single, potentially resectable site) also are excluded from enrollment.
  • 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.
  • Has a confirmed diagnosis of immunodeficiency or is receiving documented systemic steroid therapy or any other form of immunosuppressive therapy within 7 calendar days prior to the first dose of Pembrolizumab.
  • Has a known history of active Tuberculosis Bacillus (TB).
  • Hypersensitivity to Pembrolizumab or any of its excipients (L-histidine, L-histidine hydrochloride monohydrate, Sucrose or Polysorbate 80).
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  • Has had radiation therapy within 14 calendar days prior to the first dose of treatment. If subject undergone radiation, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy as per the discretion of the Qualified Investigator.
  • Has had prior chemotherapy, targeted small molecule therapy, or prior anti-cancer mAb.
  • If subject has undergone major surgery, they must have recovered adequately from the complications from the surgery prior to starting therapy as per the discretion of the Qualified Investigator.
  • 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.
  • 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 CT brain or MRI brain 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 calendar days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • 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.
  • Has a history of (non-infectious) pneumonitis or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • 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 Qualified Investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with compliance with the requirements of the trial.
  • Is pregnant or breastfeeding, or planning to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 calendar days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected).
  • Has received a live vaccine within 30 calendar days of planned start of study therapy.
  • Has previous organ and/or bone marrow transplant.

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario

Other trials in Canada

About this study

Official title: A Multi-Centre, Single Arm, Phase 2 Trial of Pembrolizumab in Treatment Naïve Patients With Poor-Prognosis Carcinoma of Unknown Primary Site

Abbreviated Title: Pembrolizumab in Patients with Poor-Prognosis Carcinoma of Unknown Primary Site (CUP) Trial Phase: 2 Clinical Indication: Treatment naïve patients with poor prognosis carcinoma of unknown primary site Trial Type: Single arm phase 2 Type of control: Not applicable Route of administration: Intravenous Trial Blinding: Not applicable Treatment Groups: 1) Pembrolizumab 200 mg IV every 3 weeks for up to 24 months. Total Number of trial subjects:25 Estimated enrollment period: 24 months Estimated duration of trial: 48 months Duration of Participation: 24 months

Read the detailed description

This is a multi-centre, single arm phase 2 study of Pembrolizumab (Keytruda™ or MK-3475) in treatment naïve patients with poor prognosis carcinoma of unknown primary site (CUP). Participants will receive Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months. Patients will be evaluated for response every 9 weeks. Patients with objective response to treatment and those with stable disease will continue to receive Pembrolizumab. Patients with tumor progression will be discontinued from the study. Patients with progressive disease (PD), but showing a clinical benefit, may continue on Pembrolizumab, as per the discretion of the responsible Qualified Investigator. Response will be evaluated as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Being tested
Pembrolizumab Injection
Keywords
CUP, Pembrolizumab, KEYTRUDA
Medical subject headings
Neoplasms, Unknown Primary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab InjectionDrug

    Also called Keytruda

    Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.

Study groups in NCT03391973
Study groupRoleWhat they receive
Arm 1 - PembrolizumabExperimentalArm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
Receives: Drug: Pembrolizumab Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR).

    The objective response rate will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST v1.1, tumor response was assessed using MRI or CT imaging. Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) as a ≥30% decrease in the sum of diameters of target lesions from baseline; Stable Disease (SD) as neither sufficient tumor shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); and PD as a ≥20% increase in the sum of diameters of target lesions or the appearance of new lesions. Disease Control Rate (DCR) was defined as the proportion of participants who achieved CR, PR, or SD as their best overall response during the assessment period, reflecting the ability of treatment to prevent disease progression. The RECIST median duration of response is the time, measured from the first date of CR or PR to PD or death.

    Measured: Within 3 years

  2. Duration of Response and Disease Control

    The duration of response and disease control will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST v1.1, tumor response was assessed using MRI or CT imaging. Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) as a ≥30% decrease in the sum of diameters of target lesions from baseline; Stable Disease (SD) as neither sufficient tumor shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease; and Progressive Disease (PD) as a ≥20% increase in the sum of diameters of target lesions (with an absolute increase of at least 5 mm) or the appearance of new lesions. Disease Control Rate (DCR) was defined as the proportion of participants who achieved CR, PR, or SD as their best overall response during the assessment period, reflecting the ability of treatment to prevent disease progression. The Duration of Response is the time, measured from the first date of CR or PR to PD or death.

    Measured: Within 3 years

  3. Incidence of Treatment-related Adverse Events (TRAEs)

    Treatment related adverse events will be assessed using CTCAE v4.0.

    Measured: Within 3 years

Secondary outcomes (2)

  1. The Overall Survival (OS) of Participants.

    OS is the time from treatment initiation to death due to any cause

    Measured: Within 4 years

  2. The Progression Free Survival (PFS) of Participants.

    Progression is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded since treatment started (nadir), with an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.

    Measured: Within 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2018
  2. Study start24 Aug 2018
  3. Primary completion16 Jun 2023
  4. Study completion12 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a multi-centre, single arm phase 2 study of Pembrolizumab (Keytruda™ or MK-3475) in treatment naïve patients with poor prognosis carcinoma of unknown primary site (CUP).
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03391973
Sponsor's protocol ID
MK-3475-418
Acronym
CUP
Status last verified
Jun 2026
First submitted
6 Nov 2017
Last updated
2 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Monzon JG, Karachiwala H, Walker J, Goel R, Wheatley-Price P, Asmis TR, Navani V, Tang PA, Vickers MM. A non-randomized phase 2 trial of pembrolizumab in untreated patients with carcinoma of unknown primary site. Eur J Cancer. 2026 May 15;239:116709. doi: 10.1016/j.ejca.2026.116709. Epub 2026 Mar 31.

    PubMed 41935492

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab Injection in people with Carcinoma of Unknown Primary, run by AHS Cancer Control Alberta at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). (time frame: Within 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03391973, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

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